Academic literature on the topic 'Tumour Tropism'
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Journal articles on the topic "Tumour Tropism"
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Lee, Soo Youn, Jung Mi Kim, Soo Young Cho, Hyun Suk Kim, Hee Sun Shin, Jeong Yong Jeon, Rukhsana Kausar, Seon Yong Jeong, Young Seek Lee, and Myung Ae Lee. "TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and integrin signalling." Biochemical Journal 459, no. 3 (April 11, 2014): 565–76. http://dx.doi.org/10.1042/bj20131119.
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Human neural stem cells possess an inherent brain tumour tropism. We identified brain tumour-derived TIMP-1 as a novel chemoattractant for human neural stem cells. TIMP-1 binding to CD63 at the plasma membrane activated β1 integrin-mediated signalling, inducing cell adhesion and migration.
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Frizziero, M., A. Malik, M. G. McNamara, S. Jamdar, R. Pihlak, A. Siriwardena, D. O'Reilly, N. De' Liguori Carino, and A. Lamarca. "Resected pancreatic ductal adenocarcinoma: understanding tumour tropism to maximise benefit from surgery." HPB 23 (2021): S228—S229. http://dx.doi.org/10.1016/j.hpb.2020.11.573.
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Shaik Fakiruddin, Kamal, Nadiah Ghazalli, Moon Lim, Zubaidah Zakaria, and Syahril Abdullah. "Mesenchymal Stem Cell Expressing TRAIL as Targeted Therapy against Sensitised Tumour." International Journal of Molecular Sciences 19, no. 8 (July 27, 2018): 2188. http://dx.doi.org/10.3390/ijms19082188.
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Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved. This might pave the way for a more effective form of combined therapy, which leads to a better treatment outcome. In this review, we first discuss the tumour-homing capacity of MSCs, its effect in tumour tropism, the different approach behind genetically-engineered MSCs, and the efficacy and safety of each agent delivered by these MSCs. Then, we focus on how sensitisation of CSCs and tumours using small molecular inhibitors can increase the effect of these cells to either TRAIL or MSC-TRAIL mediated inhibition. In the conclusion, we address a few questions and safety concerns regarding the utilization of engineered MSCs for future treatment in patients.
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Cheng, Yan, Liru Li, Dejun Wang, Qiuyan Guo, Yanan He, Tian Liang, Liyuan Sun, Xiaojun Wang, Yulei Cheng, and Guangmei Zhang. "Characteristics of Human Endometrium-Derived Mesenchymal Stem Cells and Their Tropism to Endometriosis." Stem Cells International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/4794827.
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Human endometrial tissue has become an attractive source of mesenchymal stem cells (MSCs) for cell-based therapies because these MSCs can be easily harvested and have tumour tropism as well as reduced immunogenic and inflammatory properties. Our study aimed to obtain and characterise human endometrial mesenchymal stem cells (EMSCs) and assess their endometriosis tropism. EMSCs were successfully isolated from the endometrium of women undergoing laparoscopy for idiopathic infertility. The EMSCs presented a fibroblast-like morphology during culture. Flow cytometry analyses showed that the cells were positive for the specific stem cell markers CD73, CD90, CD105, CD166, and HLA-ABC (major histocompatibility complex class I (MHC I)) but negative for CD14, CD34, CD45, and HLA-DR (MHC II). Reverse transcription polymerase chain reaction results showed that the EMSCs expressed the stem cell marker OCT4. The EMSCs could differentiate into osteocytes, adipocytes, and chondrocytes under certain conditions. The EMSCs had a high tropism to endometriosis without tumourigenicity. This study enhances the possibility of using EMSCs as drug carriers in human cell-based therapies. Meanwhile, future research could also focus on developing targeted therapies for endometriosis.
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Collins, Emma C., and Terence H. Rabbitts. "The promiscuous MLL gene links chromosomal translocations to cellular differentiation and tumour tropism." Trends in Molecular Medicine 8, no. 9 (September 2002): 436–42. http://dx.doi.org/10.1016/s1471-4914(02)02397-3.
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Yanagi, Yusuke, Makoto Takeda, and Shinji Ohno. "Measles virus: cellular receptors, tropism and pathogenesis." Journal of General Virology 87, no. 10 (October 1, 2006): 2767–79. http://dx.doi.org/10.1099/vir.0.82221-0.
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Measles virus (MV), a member of the genus Morbillivirus in the family Paramyxoviridae, is an enveloped virus with a non-segmented, negative-strand RNA genome. It has two envelope glycoproteins, the haemagglutinin (H) and fusion proteins, which are responsible for attachment and membrane fusion, respectively. Human signalling lymphocyte activation molecule (SLAM; also called CD150), a membrane glycoprotein of the immunoglobulin superfamily, acts as a cellular receptor for MV. SLAM is expressed on immature thymocytes, activated lymphocytes, macrophages and dendritic cells and regulates production of interleukin (IL)-4 and IL-13 by CD4+ T cells, as well as production of IL-12, tumour necrosis factor alpha and nitric oxide by macrophages. The distribution of SLAM is in accord with the lymphotropism and immunosuppressive nature of MV. Canine distemper virus and Rinderpest virus, other members of the genus Morbillivirus, also use canine and bovine SLAM as receptors, respectively. Laboratory-adapted MV strains may use the ubiquitously expressed CD46, a complement-regulatory molecule, as an alternative receptor through amino acid substitutions in the H protein. Furthermore, MV can infect SLAM− cells, albeit inefficiently, via the SLAM- and CD46-independent pathway, which may account for MV infection of epithelial, endothelial and neuronal cells in vivo. MV infection, however, is not determined entirely by the H protein–receptor interaction, and other MV proteins can also contribute to its efficient growth by facilitating virus replication at post-entry steps. Identification of SLAM as the principal receptor for MV has provided us with an important clue for better understanding of MV tropism and pathogenesis.
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Ohyashiki, Junko H., Tomohiro Umezu, and Kazuma Ohyashiki. "Extracellular vesicle-mediated cell–cell communication in haematological neoplasms." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1737 (November 20, 2017): 20160484. http://dx.doi.org/10.1098/rstb.2016.0484.
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Crosstalk between bone marrow tumour cells and surrounding cells, including bone marrow mesenchymal stromal cells (BM-MSCs), endothelial cells and immune cells, is important for tumour growth in haematological neoplasms. In addition to conventional signalling pathways, extracellular vesicles (EVs), which are endosome-derived vesicles containing proteins, mRNAs, lipids and miRNAs, can facilitate modulation of the bone marrow microenvironment without directly contacting non-tumourous cells. In this review, we discuss the current understanding of EV-mediated cell–cell communication in haematological neoplasms, particularly leukaemia and multiple myeloma. We highlight the actions of tumour and BM-MSC EVs in multiple myeloma. The origin of EVs, their tropism and mechanism of EV transfer are emerging issues that need to be addressed in EV-mediated cell–cell communication in haematological neoplasms. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
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Innao, Vanessa, Vincenzo Rizzo, Andrea Gaetano Allegra, Caterina Musolino, and Alessandro Allegra. "Oncolytic Viruses and Hematological Malignancies: A New Class of Immunotherapy Drugs." Current Oncology 28, no. 1 (December 25, 2020): 159–83. http://dx.doi.org/10.3390/curroncol28010019.
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The use of viruses for tumour treatment has been imagined more than one hundred years ago, when it was reported that viral diseases were occasionally leading to a decrease in neoplastic lesions. Oncolytic viruses (OVs) seem to have a specific tropism for tumour cells. Previously, it was hypothesised that OVs’ antineoplastic actions were mainly due to their ability to contaminate, proliferate and destroy tumour cells and the immediate destructive effect on cells was believed to be the single mechanism of action of OVs’ action. Instead, it has been established that oncolytic viruses operate via a multiplicity of systems, including mutation of tumour milieu and a composite change of the activity of immune effectors. Oncolytic viruses redesign the tumour environment towards an antitumour milieu. The aim of our work is to evaluate the findings present in the literature about the use of OVs in the cure of haematological neoplastic pathologies such as multiple myeloma, acute and chronic myeloid leukaemia, and lymphoproliferative diseases. Further experimentations are essential to recognize the most efficient virus or treatment combinations for specific haematological diseases, and the combinations able to induce the strongest immune response.
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STUBENRAUCH, Kay, Stefan GLEITER, Ulrich BRINKMANN, Rainer RUDOLPH, and Hauke LILIE. "Conjugation of an antibody Fv fragment to a virus coat protein: cell-specific targeting of recombinant polyoma-virus-like particles." Biochemical Journal 356, no. 3 (June 8, 2001): 867–73. http://dx.doi.org/10.1042/bj3560867.
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The development of cell-type-specific delivery systems is highly desirable for gene-therapeutic applications. Current virus-based vector systems show broad cell specificity, which results in the need to restrict the natural tropism of these viral systems. Here we demonstrate that tumour-cell-specific virus-like particles can be functionally assembled in vitro from recombinant viral coat protein expressed in Escherichia coli. The insertion of a negatively charged peptide in the HI loop of polyoma VP1 interferes with the binding of VP1 to the natural recognition site on mammalian cells and also serves as an adapter for the coupling of antibody fragments that contain complementary charged fusion peptides. A recombinant antibody fragment of the tumour-specific anti-(Lewis Y) antibody B3 could be coupled to the mutant VP1 by engineered polyionic peptides and an additional disulphide bond. With this system an entirely recombinant cell-specific delivery system assembled in vitro could be generated that transfers genes preferentially to cells presenting the tumour-specific antigen on the cell surface.
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Parkins, Katie M., Amanda M. Hamilton, Veronica P. Dubois, Suzanne M. Wong, Paula J. Foster, and John A. Ronald. "Cellular MRI Reveals Altered Brain Arrest of Genetically Engineered Metastatic Breast Cancer Cells." Contrast Media & Molecular Imaging 2019 (January 8, 2019): 1–7. http://dx.doi.org/10.1155/2019/6501231.
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Purpose. The combined use of anatomical magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging (BLI) allows for sensitive and improved monitoring of brain metastasis in preclinical cancer models. By using these complementary technologies, we can acquire measurements of viable single cell arrest in the brain after systemic administration, the clearance and/or retention of these cells thereafter, the growth into overt tumours, and quantification of tumour volume and relative cancer cell viability over time. While BLI is very useful in measuring cell viability, some considerations have been reported using cells engineered with luciferase such as increased tumour volume variation, changes in pattern of metastatic disease, and inhibition of in vivo tumour growth. Procedures. Here, we apply cellular and anatomical MRI to evaluate in vivo growth differences between iron oxide labeled naïve (4T1BR5) and luciferase-expressing (4T1BR5-FLuc-GFP) murine brain-seeking breast cancer cells. Balb/C mice received an intracardiac injection of 20,000 cells and were imaged with MRI on days 0 and 14. Mice that received 4T1BR5-FLuc-GFP cells were also imaged with BLI on days 0 and 14. Results. The number of signal voids in the brain (representing iron-labeled cancer cells) on day 0 was significantly higher in mice receiving 4T1BR5 cells compared to mice receiving 4T1BR5-FLuc-GFP cells (p<0.0001). Mice that received 4T1BR5 cells also had significantly higher total brain tumour burden and number of brain metastases than mice that received 4T1BR5-FLuc-GFP cells (p<0.0001). Conclusions. By employing highly sensitive cellular MRI tools, we demonstrate that engineered cells did not form tumours as well as their naïve counterparts, which appear to primarily be due to a reduction in cell arrest. These results indicate that engineering cancer cells with reporter genes may alter their tropism towards particular organs and highlight another important consideration for research groups that use reporter gene imaging to track metastatic cancer cell fate in vivo.
Dissertations / Theses on the topic "Tumour Tropism"
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Edge, Robert E. "Exploiting Differential Endogenous MicroRNA Expression to Enhance Oncolytic Vesicular Stomatitis Virus Tumour Tropism." Thesis, Université d'Ottawa / University of Ottawa, 2010. http://hdl.handle.net/10393/19578.
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The creation of potent oncolytic viruses (OVs) suitable for the clinic may require new strategies in virus design. Replication-competent viruses facilitate a variety of approaches to achieving tumor specificity. Altered expression of microRNAs is a common hallmark of cancer that this thesis demonstrates can be used to alter expression of a potent wild-type viral gene to achieve tumor-specific replication of an engineered vesicular stomatitis virus (VSV). Incorporation of microRNA complementary sequences (miRTs) within VSV causes reduced accumulation of miRT containing mRNAs. Let-7 miRTs introduced into the 3' untranslated region (3'UTR) of VSV matrix protein mRNA eliminate undesirable replication and associated toxicity in normal cells but permit growth in cancer cells both in vitro and in vivo. Similarly the incorporation of mir34a miRTs results in reduced in vitro VSV replication and cytotoxicity in the presence of activated p53. This thesis provides proof of concept that viruses designed to exploit the differential microRNA expression in cancer cells is a viable approach, potentially useful in optimizing oncolytic viral gene expression for maximal antitumor activity and safety.
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CRESCENTI, DANIELA. "TARGETED DELIVERY OF DIAGNOSTIC AGENTS TO NEOPLASTIC TISSUES: PRECLINICAL DEVELOPMENT OF NANOPARTICLES-BASED SYSTEMS FOR THE INTRAOPERATIVE LABELLING OF TUMOUR SITES." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/915562.
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Nonostante i progressi fatti nel campo delle terapie mediche e chirurgiche, il cancro rappresenta ancora una maggiore causa di morte nel mondo: i pazienti sviluppano spesso resistenza alle terapie antitumorali e recidive a causa della non completa deplezione di tutte le cellule tumorali. Tra le terapie antitumorali, la chirurgia mira alla rimozione completa del tessuto neoplastico, tipicamente asportato insieme ad un margine di tessuto sano non tumorale circostante allo scopo di ridurre il rischio di recidive ed aumentare la sopravvivenza dei pazienti. Tuttavia, ad oggi la procedura chirurgica di resezione tumorale manca ancora di uno strumento oggettivo in grado di mappare esattamente, nel contesto intraoperatorio, le porzioni di tessuto interessate dalla crescita neoplastica.
Scopo di questo progetto era quindi lo sviluppo preclinico di uno strumento in grado di definire e circoscrivere in maniera oggettiva l’area tumorale, per guidare i chirurghi in una rimozione intraoperatoria più sicura del tessuto tumorale.
Nello sviluppare questo progetto, ci siamo occupati dello studio di sistemi innovativi di origine naturale per la veicolazione di farmaci, chiamati Vescicole Extracellulari (EV), con i quali veicolare agenti diagnostici in maniera specifica ai siti tumorali, allo scopo di consentire la rilevazione di tumori durante l’operazione chirurgica con maggior sensibilità e precisione. Abbiamo incapsulato dei coloranti fluorescenti all’interno di vescicole extracellulari ottenute da diverse fonti biologiche e caratterizzato la biodistribuzione della fluorescenza veicolata in modelli tumorali murini tramite sistemi di imaging in vivo ed ex vivo. In questo contesto sperimentale abbiamo individuato vescicole extracellulari isolate da pazienti oncologici che
mostrano un tropismo selettivo per i tessuti neoplastici; questo tropismo tumorale risulta conservato tra vescicole extracellulari di origine tumorale ed è indipendente sia dal tipo di tumore che dalla specie di origine delle vescicole. In modelli di xenotrapianto (PDX) abbiamo dimostrato che le vescicole derivate da pazienti sono in grado di riconoscere i corrispondenti tumori umani e veicolare i traccianti fluorescenti all’interno delle cellule tumorali stesse, fornendo così una prova di principio del possibile utilizzo delle vescicole di pazienti in clinica.
Grazie all’utilizzo di tecniche omiche, abbiamo identificato una “firma” proteica caratterizzante le vescicole dei pazienti e delle molecole candidate per spiegare il meccanismo di targeting dei tumori. Da questa firma abbiamo inoltre scoperto un nuovo promettente biomarcatore per la predizione del tumore del colon-retto attraverso la biopsia liquida.
In conclusione, questo lavoro di tesi presenta la scoperta e la caratterizzazione di nanoparticelle patotropiche derivate dal sangue di pazienti oncologici come utili strumenti per la veicolazione selettiva di sostanze attive alle cellule tumorali. Le proprietà biologiche di queste vescicole autologhe e le loro innate abilità di riconoscere i tumori aprono la strada allo sviluppo di nuove strategie per diagnosi e terapie personalizzate in pazienti oncologici, dove le vescicole extracellulari vengono caricate con agenti diagnostici per la rilevazione dei tessuti neoplastici, agenti terapeutici (es. farmaci chemioterapici) per terapie antitumorali mirate o agenti teranostici per diagnosi e terapia combinate.Despite the advances made in surgical and medical therapies, cancer is still a major cause of death in the world: patients often develop resistance to therapy and relapses due to the incomplete removal of cancer cells. In cancer therapy, the surgical tumour resection aims to remove the neoplastic tissue, along with a surrounding margin of normal non-tumoral tissue, in order to reduce the risk of relapses and improve patients’ survival. However, the procedure lacks an objective tool to intraoperative map the exact portion of tissue interested by the neoplastic growth. The aim of the present project was the preclinical development of an objective tool to label and circumscribe the tumour area, to guide surgeons in the intraoperative safe removal of cancer tissues. Here, we investigated novel drug delivery systems of natural origin named Extracellular Vesicles (EV) for the specific delivery of diagnostics at tumour sites, in order to allow the detection of tumours during the surgical procedure with increased sensitivity and accuracy. We encapsulated fluorescent dyes into EV from different biological sources and characterized the biodistribution of fluorescence in mouse models of cancer by in vivo and ex vivo imaging methodologies. In this experimental setting, we have identified EV isolated from cancer patients showing a selective tropism for neoplastic tissues; this tumour tropism is conserved among EV of tumoral origin and is independent from the tumour type and the species originating the vesicles. In PDX models we demonstrated that patient-derived EV recognize corresponding human tumours and deliver fluorescent agents inside cancer cells, providing a proof-of-principle demonstration of the possible translational use of patients’ EV in clinic. Taking advantage of omics technologies, we have identified a protein “signature” characterizing the PDEVs and candidate molecules for the mechanism of tumour targeting. From this signature we also discovered a novel promising biomarker for the prediction of CRC disease in liquid biopsy. In conclusion, this thesis presents the discovery and characterization of pathotropic nanoparticles derived from the blood of oncological patients as useful drug delivery tool to selectively target cancer cells. The biological properties of these autologous EV and their innate abilities to recognize tumours pave the way to the design of novel strategies of personalized diagnosis and therapies in cancer patients, where EV are loaded with diagnostics for the detection of neoplastic tissues, therapeutics (e.g. chemotherapeutic drugs) for targeted cancer therapies or theranostics for combined diagnostic and therapy.
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Nesslany, Fabrice. "Etude de la spécificité du test des comètes in vivo : application à l'étude de produits à tropisme rénal." Lille 2, 2007. http://www.theses.fr/2007LIL2S023.
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En France, le cancer du rein représente 3 % de l'ensemble des cancers et se situe par sa fréquence au 7ème rang chez l'homme et au 9ème chez la femme. Au cours des deux dernières décennies, l'incidence des cancers du rein chez l'Homme a augmenté aussi bien aux Etats-Unis, dans les autres pays occidentaux et au Japon qu'à travers le monde. De part leurs fonctions de filtration, réabsorption et sécrétion, les reins sont effectivement exposés à des concentrations élevées de substances potentiellement néphrotoxiques qui peuvent être présentes dans l'environnement, dans le milieu professionnel ou utilisées en thérapie. A ce jour, l'évaluation de la génotoxicité d'un produit fait appel à une batterie de tests dont certains sont bien reconnus mais la recherche de nouvelles techniques capables d'identifier le(s) organe(s) cible(s) et/ou de refléter les divers mécanismes d'action mis en jeu lors d'une atteinte du matériel génétique, reste toujours d'actualité. Dans ce contexte, le test des comètes in vivo, méthode très sensible d'évaluation de la génotoxicité applicable à tout type cellulaire ou à tout tissu qui permet de quantifier, au niveau de cellules individualisées, les cassures de brins de l'ADN ainsi que les sites alcali-labiles induits par différents traitements, a été mis en oeuvre en conditions alcalines (pH>13) sur cellules isolées de rein de rat. Au cours de cette étude, nous avons tout d'abord montré que le test des comètes in vivo sur cellules isolées de rein était capable de distinguer les cancérogènes rénaux génotoxiques des cancérogènes rénaux épigénétiques alors que la cytotoxicité ne s'est pas révélée être un facteur interférant : les 5 cancérogènes rénaux agissant selon différents mécanismes génotoxiques ont été clairement détectés directement ou indirectement dans le cas du cis-platine, alors que les cancérogènes rénaux épigénétiques et les produits néphrotoxiques non-cancérogènes se sont révélés clairement négatifs. La réponse positive observée sur l'acide nitrilotriacétique, classé comme cancérogène chez le rongeur agissant par un mécanisme non génotoxique, pourrait être liée à la déprivation en cations divalents (incluant les ions Ca2+) au niveau des cellules du tractus urinaire menant à un effet clastogène local et indirect ce qui suggère l'existence d'une dose seuil au-delà de laquelle des événements générant l'apparition de tumeurs seront observés. En revanche, l'effet néphrocancérogène du tris-chloro-éthyl-phosphate est lié à son activité génotoxique intrinsèque et non à des phénomènes épigénétiques comme cela est décrit dans la littérature. Enfin, la génotoxicité organospécificique du Chloracétal C5, suspecté d'être responsable d'un excès de cancers du rein au sein de la population salariée d'une usine chimique, démontrée in vitro a été confirmée in vivo par le test des comètes. En conclusion, le test des comètes in vivo a montré une grande sensibilité et une bonne spécificité ce qui permet de l'utiliser comme outil pour évaluer le potentiel génotoxique d'un produit lorsque des changements néoplasiques/prénéoplasique ont lieu consécutivement à des traitements subchroniques ou chroniques afin de déterminer le rôle de la génotoxicité dans l'induction de tumeur, et/ou d'en étudier l'organospécificité.
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Pecheur, Isabelle. "Rôle de l'intégrine αvβ3 dans l'adressage des cellules tumorales à l'os." Lyon 1, 2002. http://www.theses.fr/2002LYO1T174.
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Delmas, Véronique. "Structure et proprietes biologiques du papovavirus de hamster." Paris 6, 1986. http://www.theses.fr/1986PA066550.
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Le papovavirus de hamster (hapv) possede un tropisme restreint in vivo vis a vis des keratinocytes et des lymphocytes. Il se replique dans les tumeurs cutanes qui apparaissent chez des hamsters syriens, et induit egalement des lymphomes chez le hamster. L'organisation genetique du hapv deduite de sa sequence a montre qu'il appartient a la famille des polyomavirus. Le hapv est present dans les lymphomes sous forme de multiples copies libres possedant toujours une deletion localisee dans la meme region du genome. Les signaux de transcription precoce du hapv semblent etre actives par la region precoce de ce virus
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Pinard, Maxime. "Nouvelle approche pour modifier le tropisme des vecteurs adénoviraux à l’aide de ligands bispécifiques." Thèse, 2011. http://hdl.handle.net/1866/8519.
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L’adénovirus a été étudié dans l’optique de développer de nouveaux traitements
pour différentes maladies. Les vecteurs adénoviraux (AdV) sont des outils intéressants du
fait qu’ils peuvent être produits en grandes quantités (1X1012 particules par millilitre) et de
par leur capacité à infecter des cellules quiescentes ou en division rapide. Les AdVs ont
subi bon nombre de modifications pour leur permettre de traiter des cellules tumorales ou
pour transporter des séquences génétiques exogènes essentielles pour le traitement de
maladies monogéniques. Toutefois, les faibles niveaux d’expression du récepteur primaire
de l’adénovirus, le CAR (récepteur à l’adénovirus et au virus coxsackie), réduit grandement
l’efficacité de transduction dans plusieurs tumeurs. De plus, certains tissus normaux comme
les muscles n’expriment que très peu de CAR, rendant l’utilisation des AdVs moins
significative. Pour pallier à cette limitation, plusieurs modifications ont été générées sur les
capsides virales. L’objectif de ces modifications était d’augmenter l’affinité des AdVs pour
des récepteurs cellulaires spécifiques surexprimés dans les tumeurs et qui seraient exempts
dans les tissus sains avoisinant. On peut mentionner dans les approches étudiées:
l’utilisation de ligands bispécifiques, l’incorporation de peptides dans différentes régions de
la fibre ou la substitution par une fibre de sérotypes différents.
Notre hypothèse était que les domaines d’interaction complémentaire (K-Coil et ECoil)
permettraient aux ligands de s’associer aux particules virales et d’altérer le tropisme
de l’AdV. Pour ce faire, nous avons inclus un domaine d’interaction synthétique, le K-Coil,dans différentes régions de la fibre virale en plus de générer des mutations spécifiques pour
abolir le tropisme naturel. Pour permettre la liaison avec les récepteurs d’intérêt dont
l’EGF-R, l’IGF-IR et le CEA6, nous avons fusionné le domaine d’interaction
complémentaire, le E-Coil, soit dans les ligands des récepteurs ciblés dont l’EGF et l’IGF-I,
soit sur un anticorps à un seul domaine reconnaissant la protéine membranaire CEA6,
l’AFAI.
Suite à la construction des différents ligands de même que des différentes fibres
virales modifiées, nous avons determiné tout d’abord que les différents ligands de même
que les virus modifiés pouvaient être produits et que les différentes composantes pouvaient
interagir ensemble. Les productions virales ont été optimisées par l’utilisation d’un nouveau
protocole utilisant l’iodixanol. Ensuite, nous avons démontré que l’association des ligands
avec le virus arborant une fibre modifiée pouvait entraîner une augmentation de
transduction de 2 à 21 fois dans différentes lignées cellulaires. À cause de la difficulté des
adénovirus à infecter les fibres musculaires occasionnée par l’absence du CAR, nous avons
cherché à savoir si le changement de tropisme pourrait accroître l’infectivité des AdVs.
Nous avons démontré que l’association avec le ligand bispécifique IGF-E5 permettait
d’accroître la transduction autant dans les myoblastes que dans les myotubes de souris.
Nous avons finalement réussi à démontrer que notre système pouvait induire une
augmentation de 1,6 fois de la transduction suite à l’infection des muscles de souriceaux
MDX. Ces résultats nous amènent à la conclusion que le système est fonctionnel et qu’il
pourrait être évalué dans des AdVs encodant pour différents gènes thérapeutiques.Adenoviruses have been studied as a way to develop new treatments for different diseases. Adenoviral vectors (AdV) are considered interesting tools for this propose, because they can be produced at high titers (1X1012 particles per millilitre) in laboratory and they have the capacity to infect non-dividing and dividing cells. AdV have been often modified in order to obtain the ability to kill tumour cells or to deliver exogenous genetic sequences essential to treat monogenic disease. However, weak expression of the primary adenovirus receptor, the CAR (Coxsackie and adenovirus receptor) reduces greatly the transduction efficiency of AdV for the tumour cells. Moreover, some normal tissues express low amount of CAR, like the skeletal muscle, reducing the appeal of using AdV as a gene delivery vehicle for this tissue. To address this problematic, many modifications were done on the adenoviral capsid. The goal of these modifications were to generate an AdV able to target specific cellular receptors that were expressed in tumour cells but not in normal cells. Several approaches were done to modify the tropism of AdV, such as incubation with a bispecific ligands, incorporation of peptides within the adenoviral fiber structure or substitution of the viral fiber with a different serotype fiber. The hypothesis of my project was to determine if an interaction domain fused within a ligand could bind the complementary domain incorporated on a virus and change the tropism of the AdV. The first step was to include a synthetic interaction domain, the K-Coil, within specific region of the adenoviral fiber, as well as inserting two point mutations to abolish the natural tropism. To target the EGF-R, IGF-IR and the CEA6, we fused the complementary interaction domain, the E-Coil, to the respective ligand known as the EGF and the IGF-I or to a single domain antibody (known as AFAI) that bind specifically to CEA6. The specific interaction between the E-Coil and K-Coil was used to associate the ligand with the fiber in order to retarget the AdV toward the selected receptor. We showed that the different ligands as well as the modified fibers could be produced and that both E-Coil and K-Coil expressing partners could interact together. We optimized the viral production by using an iodixanol purification protocol. More importantly, we clearly demonstrated that the ligand association with the fiber could increase the transduction efficiency between 2 to 21 fold against various tumour cells. The difficulty of adenovirus to infect muscle cells because of the lack of CAR expression brought us to evaluate the potential of our retargeted AdV to increase the transduction for the tissue. We showed that the use of IGF-E5 could increase the transduction efficiency in myoblasts as wells as in myotubes. We finally demonstrated that our retargeting system could increase the transduction efficiency for skeletal muscle by 1,6 fold in new born MDX mice. In conclusion, our results show that the retargeting system is indeed functional. This system could be assessed using vectors that express therapeutic genes.
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Lai, Yu-Hsiu, and 賴育秀. "The Differential Expression of Chemokines and Chemokine Receptors in Mesenchymal Stem Cells Tumor Tropism." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/89562846720929842182.
Full textAbstract:
碩士國立中興大學
生命科學院碩士在職專班
98
Mesenchymal stem cells (MSCs) are non-haematopoietic stromal cells with the ability to proliferate and differentiate into mesenchymal tissues such as bone, cartilage and adipose. Several studies indicate that systemically infused MSCs can migrate into damaged or diseased tissues, and have a lot of clinical beneficial effects. On the other hand, MSCs also have been shown to be recruited by endocrine and paracrine signals released from the tumor site. But the mechanisms underlying these phenomena remain unclear. In this study, we used in vivo imaging system (IVIS) to investigate MSCs tumor tropism in animal model. MSCs modified to express firefly luciferase were systemically injected into tumor-bearing animals (4T1 and CT26) and their non-tumor bearing counterparts. In vivo experiments showed that MSCs selectively homing to 4T1 tumor site, but not CT26 tumor-bearing site. Previous studies have indicated that MSCs are known to functionally express chemokine receptors, which might be responsible for their tumor-homing process. Therefore, we hypothesized that 4T1 may secreted a variety of chemokines to attract MSCs. To evaluate the differential expression of genes between 4T1 and CT26, the total RNA were extracted from 4T1 tumor and CT26 tumor, respectively. Subsequently, microarray analysis containing over 41,000 transcripts were performed. The differential expressed genes were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expressions of some chemokines (CCL24, CXCL1, CXCL2, CXCL7 and VEGF-C) were up-regulated in 4T1-bearing tumor. qRT-PCR was also used to examine the expression of CCR3 (receptor for CCL24), CXCR2 (receptor for CXCL1, CXCL2 and CXCL7) and VEGFR3 (receptor for VEGF-C) in MSCs. These results indicated that MSCs could homing to a specific type of tumor but not all tumors. Furthermore, CCL24, CXCL1, CXCL2, CXCL7 and VEGF-C seem to be involved in the MSCs tumor homing. To explore the role of chemokine receptors in MSCs tumor-specific homing, specific knockout or overexpression of chemokine receptors in MSCs will pursue further.
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Liao, Hsin-Wei, and 廖辛威. "Tumor tropic delivery of retrovirus vectors using adipose-derived stem cells for brain tumor treatment." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/xbew52.
Full textAbstract:
碩士國立中正大學
分子生物研究所
103
Glioblastoma multiforme (GBM) has universally poor prognosis that is thought to be related to cellular invasion into normal tissue, making localized treatments like surgery and radiation insufficient to treat the total burden of disease. Recently, stem cells have been found offering much promise as delivery vehicles for brain tumor therapy. Our previous study had confirmed the tumor-tropic migratory ability of human adipose-derived stem cells (hASC) and investigated the efficiency of hASC to deliver replicating retrovirus vector (RRV) into glioma cells in vitro and in vivo. This in vivo experiment will be repeated for validation. Our previous study also had determined the therapeutic effects of hASC-ACE-CD (RRV expressing the yeast cytosine deaminase suicide gene) by MTS assay and an orthotopic mouse model of human glioma after treatment with prodrug 5-FC. The therapeutic effect can also delay the onset of animals. To further validate this result, we will repeat this in vivo experiment, too. In order to more intuitively observe the changes in tumor size, we constructed a lentiviral vector containing near infrared fluorescent protein (iRFP) and transduced the viral vector into U87 cells followed by subcutaneous inoculation of the cells in nude mice. Then, we used the Fluorescence Molecular Tomography (FMT) to detect the iRFP signals for observation of the tumor growth and to track the effectiveness of treatment. We wish the use of hASC as the vehicle for dispersing RRV may provide a viable strategy for glioma therapy.
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Cheng, Yea Huey, and 鄭雅惠. "Using Tumor-Tropic Monocytes as a Cell-Based Delivery System of Therapeutic and Diagnostic Nanoparticles for Chemotherapy of Tumor Hypoxia." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/41676165591473244742.
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Wu, Pei-Hsuan, and 吳佩璇. "Using Tumor-Tropic Monocytes to Deliver SPION/Chlorin e6-Encapsulated Oxygen Microbubbles to Tumor Hypoxia for Improving Efficacy of the Combined Hyperthermia and Photodynamic Therapy." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/76992391564996768439.
Full textAbstract:
碩士國立清華大學
生醫工程與環境科學系
101
Abstract Tumor-homing bone marrow-derived monocytes were utilized as a cell-based vehicle to deliver chlorin e6 (Ce6)/superparamagnetic iron oxide nanoparticles (SPIONs)-loaded oxygen microbubbles to the hypoxia regions of malignant tumors for improving therapeutic efficacy of the combined hyperthermia and photodynamic therapy (PDT). The polymeric membranes of the oxygen microbubbles were mainly composed of poly(acrylic acid-co-distearin acrylate) (poly(AAc-co-DSA)) and able to efficiently carry Ce6 species and SPIONs. In the absence of pertinent external triggers the SPION/Ce6-loaded oxygen bubbles after being internalized by monocytes are found rather benign to the host, thereby allowing to retain high cell viability and migration ability with the treatment under simulated tumor microenvironments. While being co-incubated with TRAMP-C1 cells (murine prostate cancer cells) and then exposed to both high frequency magnetic field (HFMF) and NIR illumination (660 nm), the payload-containing monocytes displayed prominent performance to inhibit tumor cell proliferation. Notably, compared to only slight deposition of both free Ce6 and cargo-loaded oxygen bubbles in the tumor region of TRAMP-C1 tumor-bearing mice after i.v. injection, the tumor accumulation of SPION/Ce6-encapsulated oxygen bubbles transported via monocytes was significantly enhanced. The tumor growth of TRAMP-C1 tumor-bearing mice intravenously injected with payload-containing monocytes and then subjected to both HFMF and NIR illumination treatment was greatly inhibited. In addition, the histological examinations of tumor sections confirmed the successful cellular transport of Ce6 molecules to the tumor hypoxic regions and the pronounced in vivo cytotoxicity elicited by the NIR-triggered generation of reactive oxygen species. This work demonstrates that the cellular delivery system using tumor-tropic monocytes to carry functionalized oxygen bubbles have great potential to enhance the antitumor efficacy, particularly in hypoxia regions, by combining the hyperthermia and PDT treatment.
Book chapters on the topic "Tumour Tropism"
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Lam, Paula Y. P., and Ivy A. W. Ho. "Tumor Tropism of Mesenchymal Stem Cells." In Stem Cell Therapeutics for Cancer, 21–38. Hoboken, NJ: John Wiley & Sons, Inc, 2013. http://dx.doi.org/10.1002/9781118660423.ch3.
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Donangelo, Ines, and Shlomo Melmed. "Implication of Pituitary Tropic Status on Tumor Development." In Frontiers of Hormone Research, 1–8. Basel: KARGER, 2006. http://dx.doi.org/10.1159/000094259.
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Gonçalves de Sena Barbosa, Mateus, and Nicollas Nunes Rabelo. "Zika Virus for Brain Cancer Treatment?" In Central Nervous System Tumors [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.107476.
Full textAbstract:
Malignant brain tumors are among the most aggressive cancers with poor prognosis and no effective treatment despite all available therapies and technologies. The search for treatments for gliomas allowed the discovery that the Zika virus (ZIKV), a flavivirus, has a tropism for brain tumor cells and acts with an oncolytic effect, reaching brain tumors, in addition to stimulating the antitumor immunity of the host. Thus, it provides long-term immunity against cancer remission, reduces tumor burden, less metastasis and complete remission in some animals, consequently increases survival. There has been support that treatment with ZIKV against glioblastoma can be effective, suggesting a new future therapy that could revolutionize the prognosis of patients with brain tumors.
Conference papers on the topic "Tumour Tropism"
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Li, Yi-Nan, Chien-Wen Chang, and Chi-Shiun Chiang. "Abstract 2196: SDF-1/CXCR4 axis-mediated tumor-tropism of monocyte membrane-coated nanoparticles." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-2196.
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Mooney, Rachael, Megan Gilchrist, Yiming Weng, Alexander Annala, Sukhada Bhojane, Elizabeth Garcia, Luella Roma, et al. "Abstract A41: Harnessing neural stem cell tumor tropism for targeted nanoparticle delivery: Potential for ovarian cancer therapy." In Abstracts: AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; September 18-21, 2013; Miami, FL. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1078-0432.ovca13-a41.
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Lafci, Berkan, Elena Mercep, Joaquin L. Herraiz, Xosé Luís Deán-Ben, and Daniel Razansky. "Transmission-reflection optoacoustic ultrasound (TROPUS) imaging of mammary tumors." In Photons Plus Ultrasound: Imaging and Sensing 2021, edited by Alexander A. Oraevsky and Lihong V. Wang. SPIE, 2021. http://dx.doi.org/10.1117/12.2577907.
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Tatini, Francesca, Fulvio Ratto, Sonia Centi, Ida Landini, Stefania Nobili, Ewa Witort, Franco Fusi, Sergio Capaccioli, Enrico Mini, and Roberto Pini. "Specific markers, micro-environmental anomalies and tropism: opportunities for gold nanorods targeting of tumors in laser-induced hyperthermia." In SPIE BiOS, edited by Wolfgang J. Parak, Marek Osinski, and Kenji I. Yamamoto. SPIE, 2014. http://dx.doi.org/10.1117/12.2039413.
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Batista, Suzana Bastos, Deborah Calado Coelho, and Gabriela Coutinho Amorim. "Epilepsy in patients with COVID-19." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.179.
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Introduction: Coronavirus disease 2019 (COVID-19), caused by SARSCoV-2, appeared in a Chinese city in late 2019. Four months after its emergence it was declared by the World Health Organization as a pandemic. Although the virus has tropism for respiratory tract cells, there is evidence of involvement of systems such as vascular, digestive, hematological, urinary and nervous. Some neurological complications were observed in patients with COVID-19, such as stroke, myopathies and polyneuropathies. Encephalitis may cause seizures, suggesting that the inflammatory process by COVID-19 may be associated with seizures. Objectives: To address the possible association between seizures and SARS-CoV-2 infection. Methodology: The research is na integrative review carried out in a virtual environment, based on articles published between 2020 and 2021, with the theme “COVID-19, epilepsy and seizures”, on the academic Google platforms, SciELO portal and PubMed. Results: It is known that encephalitis and viral infections can trigger epileptic seizures by the pathophysiological mechanisms of activation of the inflammatory cascade. This process involves the release of inflammatory cytokines, tumor necrosis factor (TNF-α), interleukins 2, 6, 7 and 10, and complement, this neuronal hyper excitability activates Glutamate receptors, triggering seizures. Based on this, epileptic seizures can be explained in patients with neurological impairment by COVID-19. Conclusion: It was observed that inflammatory processes lead to excitation of receptors that trigger seizures. Therefore, the disruption of the blood brain barrier can play a fundamental role in the initiation of this process. However, the pathophysiological mechanism is not yet well elucidated, and further studies are needed on this.
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Zhang, Yun, Danielle Jernigan, Mercedes Lioni, Fernando Garcia, and Alessandro Fatatis. "Abstract 1416: An animal model to study the effects of primary tumor excision on metastatic potential and organ-tropism of residual breast cancer cells." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1416.
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