729 research outputs found
FiRe and microarrays: a fast answer to burning questions
FiRe is a user-friendly ExcelÂź macro designed to survey microarray data rapidly. This software interactively assembles data from different experiments and produces lists of candidate genes according to patterns of gene expression. Furthermore, macros bundled with FiRe can compare lists of genes, merge information from different spreadsheets, link candidates to information available from web-based databases, and produce heat-maps for easy visualization of microarray data. FiRe is freely available at http://www.unifr.ch/plantbio/FiRe/main.html
Low oxygen tension reverses antineoplastic effect of iron chelator deferasirox in human glioblastoma cells
Background
Overcoming resistance to treatment is an essential issue in many cancers including glioblastoma (GBM), the deadliest primary tumor of the central nervous system. As dependence on iron is a key feature of tumor cells, using chelators to reduce iron represents an opportunity to improve conventional GBM therapies. The aim of the present study was, therefore, to investigate the cytostatic and cytotoxic impact of the new iron chelator deferasirox (DFX) on human GBM cells in well-defined clinical situations represented by radiation therapy and mild-hypoxia.
Results
Under experimental normoxic condition (21Â % O2), deferasirox (DFX) used at 10Â ÎŒM for 3Â days reduced proliferation, led cell cycle arrest in S and G2-M phases and induced cytotoxicity and apoptosis in U251 and U87 GBM cells. The abolition of the antineoplastic DFX effects when cells were co-treated with ferric ammonium sulfate supports the hypothesis that its effects result from its ability to chelate iron. As radiotherapy is the main treatment for GBM, the combination of DFX and X-ray beam irradiation was also investigated. Irradiation at a dose of 16Â Gy repressed proliferation, cytotoxicity and apoptosis, but only in U251 cells, while no synergy with DFX was observed in either cell line. Importantly, when the same experiment was conducted in mild-hypoxic conditions (3Â % O2), the antiproliferative and cytotoxic effects of DFX were abolished, and its ability to deplete iron was also impaired.
Conclusions
Taken together, these in vitro results could raise the question of the benefit of using iron chelators in their native forms under the hypoxic conditions often encountered in solid tumors such as GBM. Developing new chemistry or a new drug delivery system that would keep DFX active in hypoxic cells may be the next step toward their application
Interactions de nanovecteurs d'agents anticancéreux avec le milieu vivant et franchissement de barriÚres biologiques
In vitro expansion of U87-MG human glioblastoma cells under hypoxic conditions affects glucose metabolism and subsequent in vivo growth
Hypoxia is a characteristic feature of solid tumors leading to the over expression of hypoxia-inducible factor (HIF)-1α protein and therefore to a specific cellular behavior. However, even though the oxygen tension in tumors is low (<5 %), most of the cell lines used in cancer studies are grown under 21 % oxygen tension. This work focuses on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-13C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose.
However, under both hypoxic and normoxic conditions, glucose is used for de novo synthesis of pyrimidine since the 13C label is found both in the uracil and ribose moieties. Labeling of the ribose ring demonstrates that U87-MG glioma cells use the reversible branch of the non-oxidative pentose
phosphate pathway. Interestingly, stereotactic implantation of U87-MG cells grown under normoxia or mild hypoxia within the striatum of nude mice led to differential growth; the cells grown under hypoxia retaining an imprint of the oxygen adaptation as their development is then slowed down
Iron metabolism: a double-edged sword in the resistance of glioblastoma to therapies
Glioblastoma (GBM), the deadliest primary tumor of the central nervous system (CNS), is a clear illustration of the resistance of cancer cells to conventional therapies. Application of combinatorial strategies able to overcome pivotal factors of GBM resistance, particularly within the resection margins, represents an essential issue. This review focuses on the role of iron metabolism in GBM progression and resistance to therapy, and the impact of its pharmaceutical modulation on the disease. Iron, through its involvement in many biological processes, is a key factor in the control of cell behavior and cancer biology. Therefore, targeting cellular iron signaling or taking advantage of its dysregulation in cancer cells may lead to new opportunities for improving treatments and drug delivery in GBM
In vivo evaluation of intracellular drug-nanocarriers infused into intracranial tumours by convection-enhanced delivery: Distribution and radiosensitisation efficacy
Reversing the Tumor Target: Establishment of a Tumor Trap
Despite the tremendous progress made in the field of cancer therapy in recent years, certain
solid tumors still cannot be successfully treated. Alongside classical treatments in the
form of chemotherapy and/or radiotherapy, targeted treatments such as immunotherapy
that cause fewer side effects emerge as new options in the clinics. However, these
alternative treatments may not be useful for treating all types of cancers, especially for
killing infiltrative and circulating tumor cells (CTCs). Recent advances pursue the trapping
of these cancer cells within a confined area to facilitate their removal for therapeutic
and diagnostic purposes. A good understanding of the mechanisms behind tumor cell
migration may drive the design of traps that mimic natural tumor niches and guide the
movement of the cancer cells. To bring this trapping idea into reality, strong efforts are
being made to create structured materials that imitate myelinated fibers, blood vessels,
or pre-metastatic niches and incorporate chemical cues such as chemoattractants or
adhesive proteins. In this review, the different strategies used (or could be used) to trap
tumor cells are described, and relevant examples of their performance are analyzed.This work was supported by the âInstitut National de la SantĂ© et de la Recherche MĂ©dicaleâ (INSERM), the University of Angers (Angers, France), the MINECO (SAF2017-83118-R), the Agencia Estatal de Investigacion (AEI, Spain), and the Fondo Europeo de Desarollo Regional (FEDER). It is also related to the LabEx IRON âInnovative Radiopharmaceuticals in Oncology and Neurologyâ as part of the French government âInvestissements dâAvenirâ program, to the INCa (Institut National du Cancer) MARENGO consortium âMicroRNA agonist and antagonist
Nanomedicines for GliOblastoma treatment: from molecular programmation to preclinical validationâ through the PL-BIO 2014-2020 grant and to the MuMoFRaT project âMulti-scale Modeling & simulation of the response to hypo-Fractionated Radiotherapy or repeated molecular radiation Therapiesâ supported by âLa RĂ©gion Pays-de-la-Loireâ and by the
CancéropÎle Grand-Ouest (tumor targeting and radiotherapy network). MN was a Ph.D. student involved in the Erasmus Mundus Joint Doctorate program for Nanomedicine and
pharmaceutical innovation (EMJD NanoFar) and received a fellowship from âLa RĂ©gion Pays-de-la-Loire.âS
External irradiation models for intracranial 9L glioma studies
<p>Abstract</p> <p>Purpose</p> <p>Radiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI) protocol for a rat 9L glioma model.</p> <p>Materials and methods</p> <p>9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed.</p> <p>Results</p> <p>Irradiated rats had significantly a longer survival (p = 0.01). No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule.</p> <p>Conclusions</p> <p>Delivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.</p
Nouvelles stratégies de radionanomédecines pour le ciblage des cellules initiatrices de cancer dans le glioblastome
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