Tag Archives: therapy

Metronomic treatment in immunocompetent preclinical glioblastoma

“Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide” by by L. Ferrer-Font,  N. Arias-Ramos, S. Lope-Piedrafita, M. Julià-Sapé , M. Pumarola, C. Arús  and A. P. Candiota. NMR Biomed. 2017. DOI: 10.1002/nbm.3748. 

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. In preceding years, efforts have focused in new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, as for example the “metronomic” approaches.

We have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/Kg) or TMZ (range 140-240 mg/Kg) metronomic administration (every 6 days) were performed in tumor-bearing mice. Tumor evolution was monitored at 7T with T2-weighted MRI, Diffusion weighted imaging and MRSI-based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6+21.0 days, n=30) compared to control (19.4+2.4 days, n=18). Also, it was found a clear edema appearance during chemotherapeutic treatment suggesting inflammatory associated processes. The necropsy performed in mice cured from GBM after high TMZ cumulative dosage (980-1400 mg/Kg) revealed lymphoma incidence.

Multi-Slice MRSI Analysis of Therapy Response in Preclinical Glioblastoma

Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment” by N. Arias-Ramos, L. Ferrer-Font,  S. Lope-Piedrafita,  V. Mocioiu, M. Julià-Sapé , M. Pumarola, C. Arús  and A. P. Candiota. Metabolites, 2017, 18;7(2). pii: E20. DOI: 10.3390/metabo7020020.

Glioblastoma (GBM) is the most common and aggressive glial primary tumor with a survival average of 14-15 months, even after application of standard treatment. Non-invasive surrogate biomarkers of therapy response may be relevant for improving patient survival. Nosological images of therapy response using a semi-supervised source extraction approach in preclinical GBM based on single slice Magnetic Resonance Spectroscopic Imaging (MRSI) was previously describe by our group. However, because of GBM heterogeneity, relevant response information could be missed just by studying one slice. Therefore, the goal of this work was to acquire 3D-like information from preclinical GBM under a longitudinal treatment protocol, using a multi-slice MRSI approach.

Nosological maps were obtained based on semi-supervised convex Non-negative Matrix Factorization and each voxel was colored according to the contribution to the spectral pattern of each one of the three sources or characteristic spectral patterns: Normal brain, actively proliferating tumour or responding tumour.

Heterogeneous response levels were observed and three arbitrary groups of treated animals were defined as: high response, intermediate response, and low response. Histopathological studies showed an inverse correlation between the responding pattern level and Ki67 proliferation rate.


Stroke Therapy in Mice

PLoSONEcover“Factors Secreted by Endothelial Progenitor Cells Enhance Neurorepair Responses after Cerebral Ischemia in Mice” by Rosell, A., Morancho, A., Navarro-Sobrino, M., Martínez-Saez, E., Hernández-Guillamon, M., Lope-Piedrafita, S., Barceló, V., Borrás, F., Penalba, A., García-Bonilla, L., Montaner, J. PLoS ONE 8 (2013), e73244. DOI: 10.1371/journal.pone.0073244

Cell therapy with endothelial progenitor cells (EPCs) has emerged as a promising strategy to regenerate the brain after stroke. Continue reading Stroke Therapy in Mice