Browsing by Subject "Astrocytoma"
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- PublicationOpen AccessArgyrophilic nucleolar organizer region (AgNOR) counting in astrocytic gliomas: prognostic value(Murcia : F. Hernández, 1996) Cardesa, Antonio; Ferreres, Joan-Carles; Figols, J.; Val-Bernal, José Fernando; Cruz Sánchez, F.F.In 87 astrocytic gliomas the number of AgNORs/nucleus was retrospectively studied and data correlated with the histological type of the tumors and survival. Al1 patients were treated by the same surgical team and with uniform criteria. Statistically significant differences (p<0.01) were found in relation with the AgNOR averages among the histological types of tumors. A statistically significant linear correlation (p<0.05) between the AgNOR values and survival of the patients was also found. Patients with mean AgNOR values higher than 2.23 and lower than 2.9 survived an average of 11.5I9.1 months vs. a sumival in average of 24.4I34.1 months with mean AgNOR values under 2.23 (p<0.05). Patients with AgNOR values higher than 2.9 survived, on average, 7.7I3.9 months. AgNOR counting in astrocytic gliomas is a reproducible, easy, quick method with prognostic value. AgNORs may be successfully applied in routine material to assess the growth potential of astrocytic gliomas.
- PublicationOpen AccessCausal probabilistic modeling for malignancy grading in pathology with explanations of dependency to the related histological features(Murcia : F. Hernández, 2007) Weidl, G.; Iglesias-Rozas, J.R.; Roehrl, N.This work demonstrates that histological grading of brain tumors and astrocytomas can be accurately predicted and causally explained with the help of causal probabilistic models, also known as Bayesian networks (BN). Although created statistically, this allows individual identification of the grade of malignancy as an internal cause that has enabled the development of the histological features to their observed state. The BN models are built from data representing 794 cases of astrocytomas with their malignant grading and corresponding histological features. The computerized learning process is improved when pre-specified knowledge (from the pathologist) about simple dependency relations to the histological features is taken into account. We use the BN models for both grading and causal analysis. In addition, the BN models provide a causal explanation of dependency between the histological features and the grading. This can offer the biggest potential for choice of an efficient treatment, since it concentrates on the malignancy grade as the cause of pathological observations. The causal analysis shows that all ten histological features are important for the grading. The histological features are causally ordered, implying that features of first order are of higher priority, e.g. for the choice of treatment in order not to allow the malignancy to progress to a higher degree. Due to the explanations of feature relations, the complement to any malignancy classification tool and allows reproducible comparison of malignancy grading.
- PublicationOpen AccessExposure to ELF-pulse modulated X band microwaves increases in vitro human astrocytoma cell proliferation(Murcia : F. Hernández, 2009) Pérez-Castejon, C.; Pérez-Bruzón, R.N.; Llorente, M.; Pes, N.; Lacasa, C.; Figols, T.; Lahoz, M.; Maestú, C.; Vera-Gil, A.; Del Moral, A.; Azanza, M.J.Common concern about the biological effects of electromagnetic fields (EMF) is increasing with the expansion of X-band microwaves (MW). The purpose of our work was to determine whether exposure to MW pulses in this range can induce toxic effects on human astrocytoma cells. Cultured astrocytoma cells (Clonetics line 1321N1) were submitted to 9.6 GHz carrier, 90% amplitude modulated by extremely low frequency (ELF)-EMF pulses inside a Gigahertz Transversal Electromagnetic Mode cell (GTEM-cell). Astrocytoma cultures were maintained inside a GTEMincubator in standard culture conditions at 37±0.1°C, 5% CO2, in a humidified atmosphere. Two experimental conditions were applied with field parameters respectively of: PW 100-120 ns; PRF 100-800 Hz; PRI 10-1.25 ms; power 0.34-0.60 mW; electric field strength 1.25-1.64 V/m; magnetic field peak amplitude 41.4-54.6 μ Oe. SAR was calculated to be 4.0x10-4 W/Kg. Astrocytoma samples were grown in a standard incubator. Reaching 70-80% confluence, cells were transferred to a GTEM-incubator. Experimental procedure included exposed human astrocytoma cells to MW for 15, 30, 60 min and 24 h and unexposed shamcontrol samples. Double blind method was applied. Our results showed that cytoskeleton proteins, cell morphology and viability were not modified. Statistically significant results showed increased cell proliferation rate under 24h MW exposure. Hsp-70 and Bcl-2 antiapoptotic proteins were observed in control and treated samples, while an increased expression of connexin 43 proteins was found in exposed samples. The implication of these results on increased proliferation is the subject of our current research.
- PublicationOpen AccessHsp27 and its expression pattern in diffusely infiltrating astrocytomas(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Mäkelä, Katri S.; Haapasalo, Joonas A.; Ilvesaro, Joanna M.; Parkkila, Seppo; Paavonen, Timo; Haapasalo, Hannu K.Aims: Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1- R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas. Methods: Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival. Results: There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p=0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively) Conclusions: Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.
- PublicationOpen AccessIDH-mutant diffuse gliomas: tips and tricks in the era of genomic tumor classification(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Ammendola, Serena; Broggi, Giuseppe; Barresi, ValeriaAccording to the fifth edition of the World Health Organization (WHO) Classification, diffuse gliomas typically occurring in adults are classified as oligodendroglioma IDH-mutant and 1p/19q codeleted, astrocytoma IDH-mutant, and glioblastoma IDHwildtype. Among these, the former has the most favorable clinical course, whereas the latter has the worst prognosis. In IDH-mutant gliomas, the IDH1 p.R132H is the most frequent IDH mutation. Other mutations in IDH1 are rare and predominantly found in astrocytomas, whereas IDH2 mutations are mostly observed in oligodendrogliomas. Astrocytomas IDHmutant display frequent immunohistochemical loss of ATRX, which is mutually exclusive with 1p/19q codeletion. They are graded based on histopathological features and the presence of CDKN2A/B homozygous deletion, whereas the criteria for grading oligodendrogliomas are less defined. DNA methylation profiling has recently shown three additional distinct tumor types among diffuse IDHmutant gliomas: infratentorial astrocytoma IDH mutant; primary mismatch repair deficient IDH-mutant astrocytoma (PMRDIA); and oligosarcoma. Infratentorial astrocytoma IDH-mutant is enriched in IDH1 or IDH2 mutations that differ from the IDH1 p.R132H mutation and are detectable only by gene sequencing, displays less frequent ATRX loss and MGMT promoter methylation than supratentorial IDH-mutant astrocytomas, and may additionally harbor the H3 K27M mutation, which is typically found in H3 K27-altered diffuse midline glioma. PMRDIA occurs in the context of primary mismatch repair deficiency, is characterized by frequent MSH6 mutations, hypermutation, low frequency of MGMT promoter methylation, and poor clinical outcomes. Finally, oligosarcoma is a tumor featuring oligodendroglial and sarcomatous areas, and is characterized by worse outcome and frequent 1p/19q copy number loss of heterozygosity.
- PublicationOpen AccessPrognostic analysis of astrocytic gliomas correlating histological parameters with the proliferating cell nuclear antigen labelling index (PCNA-LI)(Murcia : F. Hernández, 1997) Cruz-Sánchez, F. F.; Ferreres, Joan-Carles; Figols, J.; Palacín, A.; Cardesa, Antonio; Rossi, M.L.; Val-Bernal, José FernandoEighty out of 250 cases of astrocytic glioma collected from a practice served by a single clinical team over a 15-year period were studied using a full complement of clinical, follow up, histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining for the obtention of the PCNA-labelling index (LI). A statistical evaluation and discriminant analysis were carried out with the aim of clarifying the importance of various parameters as predictors of tumor behaviour. Data are correlated with survival (with a 10- year follow up). A significant correlation with survival was found when histological grouping and the PCNA-LI were studied with the Cox test. Most significant features were histological as detected using classical techniques including histological grading. The utilization of objective values (mitosis, cellular density and necrosis) appears to be useful in grading astrocytic tumors. Our results emphasize the importance of cytological, histological and PCNA-LI parameters as predictors of tumor behaviour.
- PublicationOpen AccessStandardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells(Murcia: F. Hernández, 2007) Martínez Murillo, R.; Martínez, A.Animal models of glial-derived neoplasms are needed to study the biological mechanisms of glioma tumorigenesis and those that sustain the disease state. With the aim to develop and characterize a suitable in vivo experimental mouse model for infiltrating astrocytoma, with predictable and reproducible growth patterns that recapitulate human astrocytoma, this study was undertaken to analyze the long-term course of a syngeneic orthotopically implanted CT-2A mouse astrocytoma in C57BL/6J mice. Intracranial injection of CT-2A cells into caudate-putamen resulted in development of an aggressive tumor showing typical features of human glioblastoma multiforme, sharing close histological, immunohistochemical, proliferative, and metabolic profiles. To simulate metastatic disease to the brain, CT-2A cells were injected through the internal carotid artery. Tumors identical to those obtained by intracranial injection were obtained. Finally, CT-2A cells were re-isolated from experimental brain tumors and transcranially re-injected into the caudate-putamen of healthy mice. These cells generated new tumors that were indistinguishable from the initial ones, suggesting in vivo self-renewal of tumor cells. Small-animal models are essential for testing novel biological therapies directed against relevant molecular targets. In a preliminary study, experimental CT-2A tumors were chronically treated with the small molecule 77427, a gastrin-releasing peptide (GRP) blocker compound that inhibits angiogenesis. Treated animals developed significantly smaller tumors than controls, suggesting an antitumor action for 77427 in glioblastomas. We conclude that the orthotopic CT-2A tumor model, as described herein, is appropriate to explore the mechanisms of glioma development and for preclinical trials of promising drugs.
- PublicationOpen AccessThe expression of the epitope H recognized by the monoclonal antibody H is higher in astrocytomas compared to anaplastic astrocytomas and glioblastomas(Murcia : F. Hernández, 2005) Arvanitis, D.; Arvanitis, L.; Panourias, I.G.; Kitsoulis, P.; Kanavaros, PanagiotisThe epitope H contains an O-linked Nacetylglucosamine residue in a specific conformation and/or environment recognized by the monoclonal antibody H (mAbH). mAbH stains two bands with Mr x10-3 of 209 and 62 in lysates of cultured rat astrocytes. In normal human brains epitope H is absent from the overwhelming majority of normal astrocytes and only sparse reactivity is observed, confined mostly to fibrous astrocytes. Upregulation of the epitope H takes place in reactive astrocytes. In the present study we used the mAbH to investigate the immunohistochemical expression of the epitope H in 41 cases of astrocytic tumors including 19 cases of astrocytomas, 8 cases of anaplastic astrocytomas and 14 cases of glioblastomas. Seven out of 19 cases (37%) of astrocytomas showed weak staining, 10 cases (53%) moderate staining and 2 cases (10%) intense staining. Two out of 8 cases (25%) of anaplastic astrocytomas appeared negative, 3 cases (37.5%) showed weak staining and 3 cases (37.5%) moderate staining. Four out of 14 cases (28.5) of glioblastomas appeared negative, 7 cases (50%) showed weak staining, 2 cases (14%) showed moderate staining and only one case (7.5%) showed intense staining. There was a statistically significant elevation of the expression of the epitope H in astrocytomas compared to anaplastic astrocytomas and glioblastomas (p=0.047). These results indicate that the expression of the epitope H decreases in parallel with the increase of the grade of astrocytic tumors from low to higher grade neoplasms. This could be of interest for predicting the progression of an astrocytic tumor since it is documented that astrocytomas progress to tumors of higher grade of malignancy. Further investigation of the antigens bearing the epitope H might help to gain further insight into the mechanisms which regulate the progression of astrocytic tumors and to examine the relevance of the mAbH staining with respect to the prognosis of these neoplasms.