Nuestros investigadores

María Collantes Martínez

Medicina Nuclear
Clínica Universidad de Navarra. Clínica Universidad de Navarra
Facultad de Medicina. Universidad de Navarra
Líneas de investigación
Imagen molecular en pequeños animales mediante tomografía por emisión de positrones (PET)
Índice H
15, (WoS, 15/07/2019)

Publicaciones científicas más recientes (desde 2010)

Autores: de Arcocha-Torres, M., (Autor de correspondencia); Quincoces Fernández, Gemma; Martinez-Lopez, A. L.; et al.
ISSN 2253-654X  Vol. 39  Nº 4  2020  págs. 225 - 232
Autores: Ramos Membrive, Rocio; Erhard García, Álvaro; Luis de Redín Subirá, Inés; et al.
ISSN 1773-2247  2020 
Autores: Luis de Redín Subirá, Inés; Expósito Rincón, Francisco; Agüeros Bazo, Maite; et al.
ISSN 2190-393X  Vol. 10  Nº 3  2020  págs. 635 - 645
Bevacizumab (as other monoclonal antibodies) has now become a mainstay in the treatment of several cancers in spite of some limitations, including poor tumour penetration and the development of resistance mechanisms. Its nanoencapsulation may be an adequate strategy to minimize these problems. The aim of this work was to evaluate the efficacy of bevacizumab-loaded nanoparticles (B-NP-PEG) on a xenograft model of human colorectal cancer. For this purpose, human serum albumin nanoparticles were prepared by coacervation, then coated with poly(ethylene glycol) and freeze-dried. B-NP-PEG displayed a mean size of about 300 nm and a bevacizumab loading of approximately 145 ¿g/mg. An in vivo study was conducted in the HT-29 xenograft model of colorectal cancer. Both, free and nanoencapsulated bevacizumab, induced a similar reduction in the tumour growth rate of about 50%, when compared to controls. By microPET imaging analysis, B-NP-PEG was found to be a more effective treatment in decreasing the glycolysis and metabolic tumour volume than free bevacizumab, suggesting higher efficacy. These results correlated well with the capability of B-NP-PEG to increase about fourfold the levels of intratumour bevacizumab, compared with the conventional formulation. In parallel, B-NP-PEG displayed six-times lower amounts of bevacizumab in blood than the aqueous formulation of the antibody, suggesting a lower incidence of potential undesirable side effects. In summary, albumin-based nanoparticles may be adequate carriers to promote the delivery of monoclonal antibodies (i.e. bevacizumab) to tumour tissues.
Autores: Baraibar Argota, Iosune; Román Moreno, Marta; Rodríguez Remírez, María; et al.
Revista: CANCERS
ISSN 2072-6694  Vol. 12  Nº 11  2020  págs. 31-69
Autores: Vairo C; Collantes Martínez, María; Quincoces Fernández, Gemma; et al.
ISSN 0378-5173  Vol. 569  2019 
Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99m(Tc-99m-NLC) as radiomarker, topically administered on a wound. Tc-99(m)-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.
Autores: Roman, M.; López Erdozain, María Inés; Guruceaga Martínez, Elisabet; et al.
ISSN 0008-5472  Vol. 79  Nº 3  2019  págs. 625 - 638
Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G(2)-M arrest and apoptosis in mutant KRAS LUAD cells. In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in down-regulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD. Significance: These findings highlight the prognostic significance of the transcriptional regulator Id1 in KRAS-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.
Autores: Simón, Jan; Erhard García, Álvaro; Quincoces Fernández, Gemma; et al.
ISSN 1619-7070  Vol. 46  Nº SUPPL 1  2019  págs. S316 - S316
Autores: González Aseguinolaza, Gloria; Collantes Martínez, María; Ecay Ilzarbe, Marga; et al.
ISSN 0168-8278  Vol. 70  Nº 1  2019  págs. E583
Autores: Benichou, B.; Collantes Martínez, María; Moreno Luqui, Daniel; et al.
ISSN 1525-0016  Vol. 27  Nº 4  2019  págs. 197 - 198
Autores: Rúa Gómez, Marta; Simón, Jan; Collantes Martínez, María; et al.
ISSN 1619-7070  Vol. 46  Nº SUPPL 1  2019  págs. S316 - S316
Autores: Quincoces Fernández, Gemma; Erhard García, Álvaro; Collantes Martínez, María; et al.
ISSN 1619-7070  Vol. 46  Nº SUPPL 1  2019  págs. S315 - S316
Autores: Gonzalez-Aseguinolaza, G.; Collantes Martínez, María; Moreno-Luqui, D.; et al.
ISSN 1043-0342  Vol. 30  Nº 11  2019  págs. A152 - A153
Autores: Collantes Martínez, María; Martínez Velez, Naiara; Zalacain Díez, Marta; et al.
ISSN 1471-2407  Vol. 18  Nº 1  2018  págs. 1193
BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01).
Autores: Erhard García, Álvaro; Collantes Martínez, María; Gainza, G.; et al.
ISSN 1619-7070  Vol. 45  Nº Supl. 1  2018  págs. S615
Autores: Collantes Martínez, María; Morales Lozano, María Isabel; Blanco Fernández, Laura; et al.
ISSN 1619-7070  Vol. 45  2018  págs. S565 - S566
Autores: Collantes Martínez, María; Pelacho Samper, Beatriz; García Velloso, María José; et al.
ISSN 1479-5876  Vol. 15  Nº 1  2017  págs. 56
PET/CT imaging of 18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.
Autores: Castañón Álvarez, Eduardo; Soltermann, A.; López Erdozain, María Inés; et al.
ISSN 0304-3835  Vol. 402  2017  págs. 43 - 51
Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1(+/+) mice and Idl(-/-) mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Idl significantly correlated with vimentin and other EMT-related proteins. Idl loss decreased the levels of vimentin, integrin beta 1, TGF beta 1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. (C) 2017 Elsevier B.V. All rights reserved.
Autores: Collantes Martínez, María; Barajas Vélez, Miguel Ángel; Quincoces Fernández, Gemma; et al.
ISSN 1824-4785  Vol. 61  Nº 4  2017  págs. 447 - 455
Background: The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation. Methods: A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-¿-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells. Results: Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells. Conclusions: Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.
Autores: Hernández Argüello, Miguel David; Quiceno Arias, Hernán Dario; Pascual Piedrola, Juan Ignacio; et al.
ISSN 0270-4137  Vol. 76  Nº 1  2016  págs. 3 - 12
BACKGROUND: Index lesion characterization is important in the evaluation of primary prostate carcinoma (PPC). The aim of this study was to analyze the contribution of (11) C-Choline PET/CT and the Apparent Diffusion Coefficient maps (ADC) in detecting the Index Lesion and clinically significant tumors in PPC. METHODS: Twenty-one untreated patients with biopsy-proven PPC and candidates for radical prostatectomy (RP) were prospectively evaluated by means of Ultra-High Definition PET/CT and 3T MRI, which included T2-weighted imaging (T2WI) and ADC maps obtained from diffusion weighted imaging (DWI). Independent experts analyzed all the images separately and were unaware of the pathological data. In each case, the Index lesion was defined as the largest tumor measured on histopathology (Index H). In addition, the largest lesion observed on MRI (Index MRI) and the highest avid (11) C-Choline uptake lesion (Index PET) were obtained. The Gleason scores (GS) of the tumors were determined. PET/CT and ADC map quantitative parameters were also calculated. Measures of correlation among imaging parameters as well as the sensitivity (S), specificity (Sp), negative and positive predictive values (NPV and PPV) for tumor detection were analyzed. All data was validated with the pathological study. RESULTS: In the morphological study, 139 foci of carcinoma were identified, 47 of which corresponded to clinically significant tumors (>0.5¿cm(3) ). The remaining foci presented a maximum diameter (dmax ) of 0.1¿cm¿±¿SD 0.75 and were not classified as clinically significant. Thirty-two tumors presented a GS (3¿+¿3), nine GS (3¿+¿4), and six GS (4¿+¿3). A total of 21 Index H (dmax ¿=¿1.37¿cm SD¿±¿0.61) were identified. The S, Sp, NPV, and PPV for tumor detection with PET were 100%, 70%, 83%, 100%, and for MRI were 46%, 100%, 100%, 54%, respectively. Both Index PET and Index MRI were complementary and identified 95% of the Index H when quantitative criteria were used. CONCLUSION: In spite of the fact that PET imaging has higher tumor sensitivity than MRI, (11) C-Choline PET and ADC maps have complementary roles in the evaluation of Index Lesion in PPC. Index PET and Index MRI could be complementary targets in the therapeutic planning of PPC.
Autores: Collantes Martínez, María; Serrano Mendioroz, Irantzu; Benito, M.; et al.
ISSN 0964-6906  Vol. 25  Nº 7  2016  págs. 1318 - 1327
Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.
Autores: Roman, M.; Lopez, I.; Zubiri Oteiza, Leyre; et al.
ISSN 0923-7534  Vol. 27  Nº Supl. 6  2016  págs. 1270P
Autores: Rodríguez Fraile, María Macarena; Sancho Rodriguez, Lidia; Guillén Grima, Francisco; et al.
ISSN 1619-7070  Vol. 43  2016  págs. S329 - S329
Autores: Coppiello, Giulia; Collantes Martínez, María; Sirerol-Piquer, M. S.; et al.
ISSN 0009-7322  Vol. 131  Nº 9  2015  págs. 815 - 826
Background-Microvascular endothelium in different organs is specialized to fulfill the particular needs of parenchymal cells. However, specific information about heart capillary endothelial cells (ECs) is lacking. Methods and Results-Using microarray profiling on freshly isolated ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was largely shared with skeletal muscle and adipose tissue endothelium and was enriched in genes encoding fatty acid (FA) transport-related proteins. Using gain-and loss-of-function approaches, we showed that Meox2/Tcf15 mediate FA uptake in heart ECs, in part, by driving endothelial CD36 and lipoprotein lipase expression and facilitate FA transport across heart ECs. Combined Meox2 and Tcf15 haplodeficiency impaired FA uptake in heart ECs and reduced FA transfer to cardiomyocytes. In the long term, this combined haplodeficiency resulted in impaired cardiac contractility. Conclusions-Our findings highlight a regulatory role for ECs in FA transfer to the heart parenchyma and unveil 2 of its intrinsic regulators. Our insights could be used to develop new strategies based on endothelial Meox2/Tcf15 targeting to modulate FA transfer to the heart and remedy cardiac dysfunction resulting from altered energy substrate usage.
Autores: Molinet Dronda, Francisco; Gago, B.; Quiroga-Varela, A.; et al.
ISSN 0969-9961  Vol. 77  2015  págs. 165 - 172
Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague-Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r=0.95, p<0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.
Autores: Gómez Rodríguez, Violeta; Orbe Lopategui, Josune; Martínez-Aguilar, E.; et al.
ISSN 0892-6638  Vol. 29  Nº 3  2015  págs. 960 - 972
We studied the role of matrix metalloproteinase-10 (MMP-10) during skeletal muscle repair after ischemia using a model of femoral artery excision in wild-type (WT) and MMP-10 deficient (Mmp10(-/-)) mice. Functional changes were analyzed by small animal positron emission tomography and tissue morphology by immunohistochemistry. Gene expression and protein analysis were used to study the molecular mechanisms governed by MMP-10 in hypoxia. Early after ischemia, MMP-10 deficiency resulted in delayed tissue reperfusion (10%, P < 0.01) and in increased necrosis (2-fold, P < 0.01), neutrophil (4-fold, P < 0.01), and macrophage (1.5-fold, P < 0.01) infiltration. These differences at early time points resulted in delayed myotube regeneration in Mmp10(-/-) soleus at later stages (regenerating myofibers: 30 ± 9% WT vs. 68 ± 10% Mmp10(-/-), P < 0.01). The injection of MMP-10 into Mmp10(-/-) mice rescued the observed phenotype. A molecular analysis revealed higher levels of Cxcl1 mRNA (10-fold, P < 0.05) and protein (30%) in the ischemic Mmp10(-/-) muscle resulting from a lack of transcriptional inhibition by MMP-10. This was further confirmed using siRNA against MMP-10 in vivo. Our results demonstrate an important role of MMP-10 for proper muscle repair after ischemia, and suggest that chemokine regulation such as Cxcl1 by MMP-10 is involved in muscle regeneration
Autores: Anitua, E.; Pelacho Samper, Beatriz; Prado, R. ; et al.
ISSN 0168-3659  Vol. 202  2015  págs. 31 - 39
PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. (C) 2015 Elsevier B.V. All rights reserved.
Autores: Marti Climent, Josep María; Collantes Martínez, María; Jauregui-Osoro M; et al.
ISSN 2191-219X  Vol. 15  Nº 1  2015  págs. 70
(18)F]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99m)Tc-pertechnetate but much lower than that produced by radioiodine in the form of (131)INa, (123)INa, or (124)INa.
Autores: Elizalde Arbilla, María; Urtasun Alonso, Raquel; Azcona Leiza, María Teresa; et al.
ISSN 0021-9738  Vol. 124  Nº 7  2014  págs. 2909-2920
A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4¿ (Hnf4¿), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.
Autores: Collantes Martínez, María; Peñuelas Sánchez, Iván
ISSN 1133-1747  Vol. 21  Nº 79  2014  págs. 57 - 59
Autores: Marti Climent, Josep María; Collantes Martínez, María; Prieto Azcárate, Elena; et al.
ISSN 1133-1747  Vol. 79  2014  págs. 26 - 36
La imagen preclínica engloba distintas técnicas de imagen molecular que utilizan radiaciones ionizantes, destacando la tomografía por emisión de fotón único (SPECT), la tomografía de emisión de positrones (PET) y la imagen autorradiográfica. Cada una de ellas utiliza distintas sondas que permiten obtener imágenes de una gran variedad de procesos metabólicos. En ocasiones se emplean junto a equipos de rayos X que permiten obtener imágenes anatómicas. En consecuencia, la investigación en las instalaciones de imagen molecular preclínica deberá realizarse en un contexto en el que se aplique la protección radiológica. De entre los riesgos radiológicos del personal que opera este tipo de instalaciones destaca la irradiación de las manos producida tanto por la administración de los radiotrazadores a los animales como por la manipulación de los mismos, siendo importante el entrenamiento y el uso de los blindajes. El diseño de la instalación radiactiva estará determinado por la actividad que en ella se realice. En particular dependerá tanto de las distintas técnicas de imagen molecular preclínica que se desarrollen como de la relación funcional que la instalación tenga con el resto del centro en el que se encuentre, en particular con el animalario y la unidad de radiofarmacia.
Autores: Garrido, V.; Collantes Martínez, María; Barberán, M.; et al.
ISSN 0066-4804  Vol. 58  Nº 11  2014  págs. 6660 - 6667
A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [(18)F]fluoro-deoxyglucose-MicroPET ([(18)F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [(18)F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [(18)F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches.
Autores: Riverol Fernández, Mario; Ordoñez Camblor, Cristina; Collantes Martínez, María; et al.
ISSN 0969-9961  Vol. 62  2014  págs. 250-259
Much controversy exists concerning the effect of levodopa on striatal dopaminergic markers in Parkinson's disease (PD) and its influence on functional neuroimaging. To deal with this issue we studied the impact of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and chronic levodopa administration on striatal (18)F-DOPA uptake (Ki) in an animal model of PD. The levels of several striatal dopaminergic markers and the number of surviving dopaminergic neurons in the substantia nigra (SN) were also assessed. Eleven Macaca fascicularis were included in the study. Eight animals received weekly intravenous injections of MPTP for 7weeks and 3 intact animals served as controls. MPTP-monkeys were divided in two groups. Group I was treated with placebo while Group II received levodopa. Both treatments were maintained for 11months and then followed by a washout period of 6months. (18)F-DOPA positron emission tomography (PET) scans were performed at baseline, after MPTP intoxication, following 11months of treatment, and after a washout period of 1, 3 and 6months. Monkeys were sacrificed 6months after concluding either placebo or levodopa treatment and immediately after the last (18)F-DOPA PET study. Striatal dopamine transporter (DAT) content, tyrosine hydroxylase (TH) content and aromatic l-amino acid decarboxylase (AADC) content were assessed. In Group II (18)F-DOPA PET studies performed at 3 and 6months after interrupting levodopa showed a significantly increased Ki in the anterior putamen as compared to Group I. Levodopa and placebo treated animals exhibited a similar number of surviving dopaminergic cells in the SN. Striatal DAT content was equally reduced in both groups of animals. Animals in Group I exhibited a significant decrease in TH protein content in all the striatal regions assessed. However, in Group II, TH levels were significantly reduced only in the anterior and posterior putamen. Surprisingly, in the levodopa-treated animals the TH levels in the posterior putamen were significantly lower than those in the placebo group. AADC levels in MPTP groups were similar to those of control animals in all striatal areas analyzed. This study shows that chronic levodopa administration to monkeys with partial nigrostriatal degeneration followed by a washout period induces modifications in the functional activity of the dopaminergic nigrostriatal pathway.
Autores: Blesa de los Mozos, Francisco Javier; Pifl, C; Sánchez-González M.A.; et al.
ISSN 0969-9961  Vol. 48  Nº 1  2012  págs. 79 - 91
Autores: Pañeda Rodríguez, María Astrid; Collantes Martínez, María; Beattie, SG; et al.
Revista: Human Gene Therapy (Print)
ISSN 1043-0342  Vol. 22  Nº 8  2011  págs.  999-1009
Autores: Aranguren López, Xabier; Pelacho Samper, Beatriz; Peñuelas Sánchez, Iván; et al.
ISSN 0963-6897  Vol. 20  Nº 2  2011  págs. 259 - 269
There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133(+) cells and multipotent adult progenitor cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133(+) cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days posttransplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133(+)-injected animals. While transplantation of hAC133(+) cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis, and improved muscle regeneration. Incorporation of differentiated MC 133(+) or hMAPC progeny into new vessels was limited; however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-conditioned, but not hAC133(+)-conditioned, media stimulated vascular cell proliferation and prevented myoblast, endothelial, and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133(+) cell and hMAPC transplantation both contribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer term functional improvement.
Autores: Areses Elizalde, Paloma; Agüeros Bazo, Maite; Quincoces Fernández, Gemma; et al.
Revista: Molecular Imaging and Biology
ISSN 1536-1632  Vol. 13  Nº 6  2011  págs. 1215 - 1223
Autores: Marti Climent, Josep María; Prieto Azcárate, Elena; Collantes Martínez, María; et al.
Revista: Radiation Measurements
ISSN 1350-4487  Vol. 46  Nº 11  2011  págs. 1307 - 1309
This study focuses on the occupational doses of technologists working at an Animal Research Unit using PET radiotracers and on the environmental dose rates produced by the animals (mice, rats and monkeys). In particular, whole body and extremity monitoring is reported and related with the workload. The study shows that doses not only depend on the amount of activity injected but also on the type of animals and radiotracers managed. The extremities, with a great variability of the doses received, are the limiting organs as far as regulatory dose limits for workers are concerned. Mean H¿(10) rates in contact and at 20 cm from the animals, when they are handled by the technologist, range from around 1 mSv/h to 20 ¿Sv/h, respectively.
Autores: Prieto Azcárate, Elena; Collantes Martínez, María; Delgado, M; et al.
Revista: European Journal of Nuclear Medicine & Molecular Imaging
ISSN 1619-7070  Vol. 38  Nº 12  2011  págs. 2228 - 2237
This study demonstrates that any difference detected with SPM analysis of MOSAIC PET images of rat brain is detected also by the gold standard autoradiographic technique, confirming that this methodology provides reliable results, although partial volume effects might make it difficult to detect slight differences in small regions.
Autores: Mazo Vega, Manuel María; Gavira Gómez, Juan José; Abizanda Sarasa, Gloria María; et al.
ISSN 0963-6897  Vol. 19  Nº 3  2010  págs. 313 - 328
The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 10(6) GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and (18)F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 +/- 2.01% to 46.61 +/- 3.7%, p <0.05; MSC: 27.5 +/- 1.28% to 38.8 +/- 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by (18)F-FDG uptake (71.15 +/- 1.27 to 76.31 +/- 1.11, p<0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI.
Autores: Becerril Mañas, Sara; Rodríguez Murueta-Goyena, Amaia; Catalán Goñi, Victoria; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 5  Nº 6  2010  págs. e10962
BACKGROUND: Leptin and nitric oxide (NO) on their own participate in the control of non-shivering thermogenesis. However, the functional interplay between both factors in this process has not been explored so far. Therefore, the aim of the present study was to analyze the impact of the absence of the inducible NO synthase (iNOS) gene in the regulation of energy balance in ob/ob mice. METHODS AND FINDINGS: Double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes were generated, and the expression of molecules involved in the control of brown fat cell function was analyzed by real-time PCR, western-blot and immunohistochemistry. Twelve week-old DBKO mice exhibited reduced body weight (p<0.05), decreased amounts of total fat pads (p<0.05), lower food efficiency rates (p<0.05) and higher rectal temperature (p<0.05) than ob/ob mice. Ablation of iNOS also improved the carbohydrate and lipid metabolism of ob/ob mice. DBKO showed a marked reduction in the size of brown adipocytes compared to ob/ob mutants. In this sense, in comparison to ob/ob mice, DBKO rodents showed an increase in the expression of PR domain containing 16 (Prdm16), a transcriptional regulator of brown adipogenesis. Moreover, iNOS deletion enhanced the expression of mitochondria-related proteins, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1alpha), sirtuin-1 (Sirt-1) and sirtuin-3 (Sirt-3). Accordingly, mitochondrial uncoupling proteins 1 and 3 (Ucp-1 and Ucp-3) were upregulated in brown adipose tissue (BAT) of DBKO mice as compared to ob/ob rodents. CONCLUSION: Ablation of iNOS improved the energy balance of ob/ob mice by decreasing food efficiency through an increase in thermogenesis. These effects may be mediated, in part, through the recovery of the BAT phenotype and brown fat cell function improvement.
Autores: Díaz Díaz, Roque; Nguewa Kamsu, Paul; Parrondo, R; et al.
ISSN 1471-2407  Vol. 10  Nº 188  2010  págs. 1 - 10
Autores: Blesa de los Mozos, Francisco Javier; Juri Clavería, Carlos Andrés; Collantes Martínez, María; et al.
Revista: Neurobiology of Disease
ISSN 0969-9961  Vol. 38  Nº 3  2010  págs. 456 - 463
Autores: Fontanellas Roma, Antonio; Hervas Stubbs, Sandra; Mauleón Mayora, Itsaso; et al.
Revista: Molecular Therapy
ISSN 1525-0016  Vol. 18   Nº 4  2010  págs. 754 - 765