An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

Canine tumors are valuable comparative models for human counterparts, especially to explore novel biomarkers and to understand pathways and processes involved in metastasis. Vasculogenic mimicry (VM) is a unique property of malignant cancer cells which promote metastasis. Thus, it represents an opportunity to investigate both the molecular mechanisms and the therapeutic targets of a crucial phenotypic malignant switch. Although this biological process has been largely investigated in different human cancer types, including osteosarcoma, it is still largely unknown in veterinary pathology, where it has been mainly explored in canine mammary tumors. The presence of VM in human osteosarcoma is associated with poor clinical outcome, reduced patient survival, and increased risk of metastasis and it shares the main pathways involved in other type of human tumors. This review illustrates the main findings concerning the VM process in human osteosarcoma, search for the related current knowledge in canine pathology and oncology, and potential involvement of multiple pathways in VM formation, in order to provide a basis for future investigations on VM in canine tumors

Consciousness and cortical responsiveness: a within-state study during non-rapid eye movement sleep.

When subjects become unconscious, there is a characteristic change in the way the cerebral cortex responds to perturbations, as can be assessed using transcranial magnetic stimulation and electroencephalography (TMS-EEG). For instance, compared to wakefulness, during non-rapid eye movement (NREM) sleep TMS elicits a larger positive-negative wave, fewer phase-locked oscillations, and an overall simpler response. However, many physiological variables also change when subjects go from wake to sleep, anesthesia, or coma. To avoid these confounding factors, we focused on NREM sleep only and measured TMS-evoked EEG responses before awakening the subjects and asking them if they had been conscious (dreaming) or not. As shown here, when subjects reported no conscious experience upon awakening, TMS evoked a larger negative deflection and a shorter phase-locked response compared to when they reported a dream. Moreover, the amplitude of the negative deflection-a hallmark of neuronal bistability according to intracranial studies-was inversely correlated with the length of the dream report (i.e., total word count). These findings suggest that variations in the level of consciousness within the same physiological state are associated with changes in the underlying bistability in cortical circuits

EEG-based effective connectivity distinguishes between unresponsive states with and without report of conscious experience and correlates with brain complexity

Objective methods for distinguishing conscious from unconscious states in humans are of key importance for clinical evaluation of general anesthesia and patients with disorders or consciousness. Here, we test the generalizability of a DTF-based algorithm - a measure of effective connectivity - as an objective measure of conscious experience during anesthesia and correlate it with a well-tested index of consciousness: the Perturbational Complexity Index (PCI). We reanalyzed EEG data from an experimental study in which 18 healthy volunteers were randomly assigned to one of three types of general anesthesia: propofol, xenon, and ketamine. EEG was recorded before and during anesthesia, and DTF was calculated from every 1-second segment of the EEG data to quantify the effective connectivity between channel pairs. This was used to classify the state of each participant as either conscious or unconscious, and the classifications were compared with the participant’s delayed report of experience, and the PCI. The algorithm was more likely to classify participants as conscious in the awake state than during propofol and xenon anesthesia (p0.05). Furthermore, the DTF-based confidence of being classified as conscious was highly correlated with PCI (r2=0.48, p<0.05). These results provide further support for the notion that effective connectivity measured between EEG electrodes can be used to distinguish between conscious and unconscious states in humans

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness.European Union's Horizon 2020 Research and Innovation ProgrammeHermann and Lilly Schilling FoundationGerman Research FoundationCenter for Nanoscale Microscopy and Molecular Physiology of the BrainNational Institutes of Health/National Institute of Neurological Disorders and StrokeSao Paulo Research FoundationJames S. McDonnell Foundation Scholar AwardEU Grant H2020-FETOPENCanadian Institute for Advanced ResearchAzrieli Program in Brain, Mind and ConsciousnessFLAG-ERA JTC project CANONNorwegian Research CouncilNetherlands Organization for Scientific ResearchUniv Oslo, Inst Basal Med Sci, Div Physiol, Dept Mol Med, POB 1103 Blindern, N-0317 Oslo, NorwayUniv Wisconsin, Dept Neurol, Madison, WI 53705 USAUniv Wisconsin, Dept Psychiat, Madison, WI 53719 USAUniv Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniv Milan, Dept Biomed & Clin Sci Luigi Sacco, I-20157 Milan, ItalyFdn Don Carlo Gnocchi ONLUS, Ist Ricovero & Cura Carattere Sci, I-20162 Milan, ItalyUniv Amsterdam, Swammerdam Inst Life Sci, Cognit & Syst Neurosci Grp, NL-1098 XH Amsterdam, NetherlandsUniv Amsterdam, Res Prior Program Brain & Cognit, NL-1098 XH Amsterdam, NetherlandsUniv Med Goettingen, Dept Cognit Neurol, D-37075 Gottingen, GermanyLeibniz Inst Primate Res, German Primate Ctr, D-37077 Gottingen, GermanyLeibniz Sci Campus Primate Cognit, D-37077 Gottingen, GermanyUniv Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, BrazilEuropean Union's Horizon 2020 Research and Innovation Programme: 720270German Research Foundation: WI 4046/1-1National Institutes of Health/National Institute of Neurological Disorders and Stroke: 1R03NS096379FAPESP: 2016/08263-9EU Grant H2020-FETOPEN: RIA 686764Web of Scienc

Studying functional networks in human brain through intracerebral spontaneous EEG

none6G.Arnulfo; A.Pigorini; M.Massimini; L.Nobili; A.Schenone; M.M. FatoArnulfo, Gabriele; Pigorini, A.; Massimini, M.; Nobili, L.; Schenone, Andrea; Fato, MARCO MASSIM

Are the neural correlates of consciousness in the front or in the back of the cerebral cortex? Clinical and neuroimaging evidence

The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues

Global and local complexity of intracranial EEG decreases during NREM sleep

Key to understanding the neuronal basis of consciousness is the characterisation of the neural signatures of changes in level of consciousness during sleep. Here we analysed three measures of dynamical complexity on spontaneous depth electrode recordings from 10 epilepsy patients during wakeful rest and different stages of sleep: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability over time of the set of channels active above a threshold; (iii) synchrony coalition entropy, which measures the variability over time of the set of synchronous channels. When computed across sets of channels that are broadly distributed across multiple brain regions, all 3 measures decreased substantially in all participants during early-night non-rapid eye movement (NREM) sleep. This decrease was partially reversed during late-night NREM sleep, while the measures scored similar to wakeful rest during rapid eye movement (REM) sleep. This global pattern was in almost all cases mirrored at the local level by groups of channels located in a single region. In testing for differences between regions, we found elevated signal complexity in the frontal lobe. These differences could not be attributed solely to changes in spectral power between conditions. Our results provide further evidence that the level of consciousness correlates with neural dynamical complexity