scholarly journals Identification of Apolipoprotein A-II in Cerebrospinal Fluid of Pediatric Brain Tumor Patients by Protein Expression Profiling

2006 ◽  
Vol 52 (8) ◽  
pp. 1501-1509 ◽  
Author(s):  
Judith M de Bont ◽  
Monique L den Boer ◽  
Roel E Reddingius ◽  
Jaap Jansen ◽  
Monique Passier ◽  
...  

Abstract Background: Our aim was to detect differences in protein expression profiles of cerebrospinal fluid (CSF) from pediatric patients with and without brain tumors. Methods: We used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry and Q10 ProteinChip arrays to compare protein expression profiles of CSF from 32 pediatric brain tumor patients and 70 pediatric control patients. A protein with high discriminatory power was isolated and identified by subsequent anion-exchange and reversed-phase fractionation, gel electrophoresis, and mass spectrometry. The identity of the protein was confirmed by Western blotting and immunohistochemistry. Results: Of the 247 detected protein peak clusters, 123 were differentially expressed between brain tumor and control patients with a false discovery rate of 1%. Double-loop classification analysis gave a mean prediction accuracy of 88% in discriminating brain tumor patients from control patients. From the 123 clusters, a highly overexpressed protein peak cluster in CSF from brain tumor patients was selected for further analysis and identified as apolipoprotein A-II. Apolipoprotein A-II expression in CSF was correlated with the CSF albumin concentration, suggesting that the overexpression of apolipoprotein A-II is related to a disrupted blood–brain barrier. Conclusions: SELDI-TOF mass spectrometry can be successfully used to find differentially expressed proteins in CSF of pediatric brain tumor and control patients. Apolipoprotein A-II is highly overexpressed in CSF of pediatric brain tumor patients, which most likely is related to a disrupted blood–brain barrier. Ongoing studies are aimed at finding subtype specific proteins in larger groups of pediatric brain tumor patients.

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Florian Wedel ◽  
Ulrich-Wilhelm Thomale ◽  
Ingo Steffen ◽  
Arend Koch ◽  
...  

Abstract Background MRI has shortcomings in differentiation between tumor tissue and post-therapeutic changes in pretreated brain tumor patients. Patients We assessed 22 static FET-PET/CT-scans of 17 pediatric patients (median age 12 years, range 2–16 years, ependymoma n=4, medulloblastoma n=4, low-grade glioma n=6, high-grade glioma n=3, germ cell tumor n=1, choroid plexus tumor n=1, median follow-up: 112 months) with multimodal treatment. Method FET-PET/CT-scans were analyzed visually by 3 independent nuclear medicine physicians. Additionally quantitative FET-Uptake for each lesion was determined by calculating standardized uptake values (SUVmaxT/SUVmeanB, SUVmeanT/SUVmeanB). Histology or clinical follow-up served as reference. Results Static FET-PET/CT reliably distinguished between tumor tissue and post-therapeutic changes in 16 out of 17 patients. It identified correctly vital tumor tissue in 13 patients and post-therapeutic changes in 3 patients. SUV-based analyses were less sensitive than visual analyses. Except from a choroid plexus carcinoma, all tumor entities showed increased FET-uptake. Discussion Our study comprises a limited number of patients but results corroborate the ability of FET to detect different brain tumor entities in pediatric patients and discriminate between residual/recurrent tumor and post-therapeutic changes. Conclusions We observed a clear benefit from additional static FET-PET/CT-scans when conventional MRI identified equivocal lesions in pretreated pediatric brain tumor patients. These results warrant prospective studies that should include dynamic scans.


2020 ◽  
Author(s):  
Simon Ngao Mule ◽  
Andrè Guillherme da Costa Martins ◽  
Livia Rosa-Fernandes ◽  
Gilberto Santos de Oliveira ◽  
Carla Monadeli Rodrigues ◽  
...  

AbstractThe etiological agent of Chagas disease, Trypanosoma cruzi, is subdivided into seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution justifies the concerted efforts towards understanding the population structure of T. cruzi strains. In this study, we introduce a novel approach termed ‘phyloquant’ to infer the evolutionary relationships and assignment of T. cruzi strains to their DTUs based on differential protein expression profiles evidenced by bottom up large scale mass spectrometry-based quantitative proteomic features. Mass spectrometry features analyzed using parsimony (MS1, iBAQ and LFQ) showed a close correlation between protein expression and T. cruzi DTUs and closely related trypanosome species. Although alternative topologies with minor differences between the three MS features analyzed were demonstrated, we show congruence to well accepted evolutionary relationships of T. cruzi DTUs; in all analyses TcI and Tcbat were sister groups, and the parental nature of genotype TcII and the hybrid genotypes TcV/TcVI were corroborated. Character mapping of genetic distance matrices based on phylogenetics and phyloquant clustering showed statistically significant correlations. We propose the first quantitative shotgun proteomics approach as a complement strategy to the genetic-based assignment of T. cruzi strains to DTUs and evolutionary inferences. Moreover, this approach allows for the identification of differentially regulated and strain/DTU/species-specific proteins, with potential application in the identification of strain/DTU specific biomarkers and candidate therapeutic targets. In addition, the correlation between multi-gene protein expression and divergence of trypanosome species was evaluated, adding another level to understand the genetic subdivisions among T. cruzi DTUs.


2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i179-i179
Author(s):  
Jeffrey Gross ◽  
Stephanie Powell ◽  
Frank Zelko ◽  
William Hartsell ◽  
Stewart Goldman ◽  
...  

2019 ◽  
Vol 105 (3) ◽  
pp. 664-673 ◽  
Author(s):  
Kristofer W. Roberts ◽  
Hok Seum Wan Chan Tseung ◽  
Laurence J. Eckel ◽  
William S. Harmsen ◽  
Chris Beltran ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 674
Author(s):  
Diana Valeria Rossetti ◽  
Luca Massimi ◽  
Claudia Martelli ◽  
Federica Vincenzoni ◽  
Susanna Di Silvestre ◽  
...  

Ependymoma pediatric brain tumor occurs at approximate frequencies of 10–15% in supratentorial and 20–30% in posterior fossa regions. These tumors have an almost selective response to surgery and relative and confirmed resistance to radiotherapy and chemotherapic agents, respectively. Alongside histopathological grading, clinical and treatment evaluation of ependymomas currently consider the tumor localization and the genomic outlined associated molecular subgroups, with the supratentorial and the posterior fossa ependymomas nowadays considered diverse diseases. On these grounds and in trying to better understand the molecular features of these tumors, the present investigation aimed to originally investigate the proteomic profile of pediatric ependymoma tissues of different grade and localization by mass spectrometry platforms to disclose potential distinct protein phenotypes. To this purpose, acid-soluble and acid-insoluble fractions of ependymoma tumor tissues homogenates were analyzed by LC-MS following both the top-down and the shotgun proteomic approaches, respectively, to either investigate the intact proteome or its digested form. The two approaches were complementary in profiling the ependymoma tumor tissues and showed distinguished profiles for supratentorial and posterior fossa ependymomas and for WHO II and III tumor grades. Top-down proteomic analysis revealed statistically significant higher levels of thymosin beta 4, 10 kDa heat shock protein, non-histone chromosomal protein HMG-17, and mono-/uncitrullinated forms ratio of the glial fibrillary acidic protein (GFAP) fragment 388–432 in supratentorial ependymomas—the same GFAP fragment as well as the hemoglobin alpha- and the beta-chain marked grade II with respect to grade III posterior fossa ependymomas. Gene ontology classification of shotgun data of the identified cancer and the non-cancer related proteins disclosed protein elements exclusively marking tumor localization and pathways that were selectively overrepresented. These results, although preliminary, seem consistent with different protein profiles of ependymomas of diverse grade of aggressiveness and brain region development and contributed to enlarging the molecular knowledge of this still enigmatic tumor.


2009 ◽  
Vol 41 (3) ◽  
pp. 192-194 ◽  
Author(s):  
Yoshimi Sogawa ◽  
Li Kan ◽  
Adam S. Levy ◽  
Joseph Maytal ◽  
Shlomo Shinnar

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