ABSTRACT
The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGFß signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic sur.
ABSTRACT
BACKGROUND: One of the greatest neuro-oncological concern remains the lack of knowledge about the etiopathogenesis and physiopathology of gliomas. Several studies reported a strict correlation between radiological features and biological behaviour of gliomas; in this way the velocity of diametric expansion (VDE) correlate with lower grade glioma aggressiveness. However, there are no the same strong evidences for high grade gliomas (HGG) because of the lack of several preoperative MRI. PATIENTS AND METHODS: We describe a series of 4 patients affected by HGG followed from 2014 to January 2019. Two patients are male and two female; two had a pathological diagnosis of glioblastoma (GBM), one of anaplastic astrocytoma (AA) and one had a neuroradiological diagnosis of GBM. The VDE and the acceleration time (AT) was calculated for fluid attenuated inversion recovery (FLAIR) volume and for the enhancing nodule (EN). Every patients underwent sequential MRI study along a mean period of 413 days. RESULTS: Mean VDE evaluated on FLAIR volume was 39.91 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 282.7%. Median appearance time of EN after first MRI scan was 432 days. Mean VDE was 45.02 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 257.52%. CONCLUSIONS: To our knowledge, this is the first report on VDE and acceleration growth in HGG confirming their strong aggressiveness. In a case in which we need to repeat an MRI, time between consecutive scans should be reduced to a maximum of 15-20 days and surgery should be executed as soon as possible.
