Metastasis, the leading cause of cancer deaths, is an intricate process involving many important tumor and stromal proteins that have yet to be fully defined. This review discusses critical ...components necessary for the metastatic cascade, including hypoxia, inflammation, and the tumor microenvironment. More specifically, this review focuses on tumor cell and stroma interactions, which allow cell detachment from a primary tumor, intravasation to the blood stream, and extravasation at a distant site where cells can seed and tumor metastases can form. Central players involved in this process and discussed in this review include integrins, matrix metalloproteinases, and soluble growth factors/matrix proteins, including the connective tissue growth factor and lysyl oxidase.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Frontotemporal Dementias Finger, Elizabeth C
Continuum (Minneapolis, Minn.),
2016-April, 2016-Apr, 2016-04-00, 20160401, Volume:
22, Issue:
2, Dementia
Journal Article
Open access
PURPOSE OF REVIEW:This article reviews the common behavioral and cognitive features of frontotemporal dementia (FTD) and related disorders as well as the distinguishing clinical, genetic, and ...pathologic features of the most common subtypes.
RECENT FINDINGS:Advances in clinical phenotyping, genetics, and biomarkers have enabled improved predictions of the specific underlying molecular pathology associated with different presentations of FTD. Evaluation of large international cohorts has led to recent refinements in diagnostic criteria for several of the FTD subtypes.
SUMMARY:The FTDs are a group of neurodegenerative disorders featuring progressive deterioration of behavior or language and associated pathology in the frontal or temporal lobes. Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are(1) behavioral variant of FTD, (2) semantic variant primary progressive aphasia, (3) nonfluent agrammatic variant primary progressive aphasia, (4) corticobasal syndrome, (5) progressive supranuclear palsy, and (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.
Significance Here we report a fundamental and previously unknown role for the receptor tyrosine kinase AXL as a direct hypoxia-inducible transcription factor target driving the aggressive phenotype ...in renal clear cell carcinoma through the regulation of the SRC proto-oncogene nonreceptor tyrosine kinase and the MET proto-oncogene receptor tyrosine kinase. Of therapeutic relevance, we demonstrate that inactivation of growth arrest-specific 6 (GAS6)/AXL signaling using a soluble AXL decoy receptor reversed the invasive and metastatic phenotype of clear cell renal cell carcinoma (ccRCC) cells. Furthermore, we define a pathway by which GAS6/AXL signaling utilizes lateral activation of MET through SRC to maximize cellular invasion. Our data provide an alternative model for SRC and MET activation by GAS6 in ccRCC and identify AXL as a therapeutic target driving the aggressive phenotype in renal clear cell carcinoma.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Sense of Agency (SoA) refers to the feeling of control over voluntary actions and the outcomes of those actions. Several brain disorders are characterized by an abnormal SoA. To date, there is no ...robust treatment for aberrant agency across disorders; this is, in large part, due to gaps in our understanding of the cognitive mechanisms and neural correlates of the SoA. This apparent gap stems from a lack of synthesis in established findings. As such, the current review reconciles previously established findings into a novel neurocognitive framework for future investigations of the SoA in brain disorders, which we term the Agency in Brain Disorders Framework (ABDF). In doing so, we highlight key top-down and bottom-up cues that contribute to agency prospectively (i.e., prior to action execution) and retrospectively (i.e., after action execution). We then examine brain disorders, including schizophrenia, autism spectrum disorders (ASD), obsessive-compulsive disorders (OCD), and cortico-basal syndrome (CBS), within the ABDF, to demonstrate its potential utility in investigating neurocognitive mechanisms underlying phenotypically variable presentations of the SoA in brain disorders.
•Brain disorders are associated with an aberrant sense of agency (SoA).•Treatment for aberrant SoA is hindered by a well-formed conceptualization of SoA.•We propose a novel neurocognitive framework for assessing SoA in brain disorders.•We demonstrate the utility of our framework by applying it to schizophrenia, ASDs, OCDs, and cortico-basal syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hoarding and obsessive-compulsive behaviours (OCB) are well documented symptoms in frontotemporal dementia (FTD). While contemporary models consider hoarding and obsessive-compulsive disorder ...distinct, the related behaviours have not been separately examined in patients with FTD, and the neuroanatomical correlates of hoarding in patients with FTD have not been previously examined (American Psychiatric Association, 2013; Grisham and Baldwin, 2015; Mataix-Cols et al., 2010).
Patients with FTD who were evaluated between 2004 and 2018 at our centre were included. Cortical thickness and subcortical volumetric analyses were completed on available T1 high resolution anatomic scans using FreeSurfer.
Eighty-seven patients met inclusion criteria, and 49 had scans available for quantitative MRI volumetric analysis. New hoarding behaviours were present in 29% of patients and were more common in the semantic variant subtype of FTD, while 49% of individuals had new or increased OCB. Hoarding behaviours were associated with decreased thickness in a factor comprised of left temporal, insular and anterior cingulate cortices. The presence of OCB was predicted by reduced cortical thickness and volumes in a factor comprised of the anterior cingulate and subcortical volumes in the bilateral amygdala and hippocampus. OCB were associated with greater right temporal cortical thickness in comparison to patients with hoarding.
The association of the semantic variant with hoarding, together with the observed associations between left temporal atrophy and hoarding indicate that degeneration of the left temporal lobe has a role in the emergence of hoarding in FTD. As in current models of Hoarding disorder and Obsessive–Compulsive disorder, our results suggest that in patients with FTD, hoarding and OCB are clinically and anatomically partially dissociable phenomenon. The results may also help to further elucidate the cognitive processes and neural networks contributing to Hoarding disorder and Obsessive–Compulsive disorder in persons without dementia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Guilt is a negative emotion elicited by realizing one has caused actual or perceived harm to another person. One of guilt's primary functions is to signal that one is aware of the harm that was ...caused and regrets it, an indication that the harm will not be repeated. Verbal expressions of guilt are often deemed insufficient by observers when not accompanied by nonverbal signals such as facial expression, gesture, posture, or gaze. Some research has investigated isolated nonverbal expressions in guilt, however none to date has explored multiple nonverbal channels simultaneously. This study explored facial expression, gesture, posture, and gaze during the real-time experience of guilt when response demands are minimal. Healthy adults completed a novel task involving watching videos designed to elicit guilt, as well as comparison emotions. During the video task, participants were continuously recorded to capture nonverbal behaviour, which was then analyzed via automated facial expression software. We found that while feeling guilt, individuals engaged less in several nonverbal behaviours than they did while experiencing the comparison emotions. This may reflect the highly social aspect of guilt, suggesting that an audience is required to prompt a guilt display, or may suggest that guilt does not have clear nonverbal correlates.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Youths with high levels of callous-unemotional (CU) traits and aggression are at an increased risk for developing antisocial behaviours into adulthood. In this population, neurostructural grey matter ...abnormalities have been observed in the prefrontal cortex. However, the directionality of these associations is inconsistent, prompting some to suggest they may vary across development. Although similar neurodevelopmental patterns have been observed for other disorders featuring emotional and behavioural dysregulation, few studies have tested this hypothesis for CU traits, and particularly not for aggression subtypes. The current study sought to examine grey matter correlates of CU traits and aggression (including its subtypes), and then determine whether these associations varied by age. Fifty-four youths (10-19 years old) who were characterized for CU traits and aggression underwent MRI. Grey matter volume and surface area within the anterior cingulate cortex was positively associated with CU traits. The correlation between CU traits and medial orbitofrontal cortex (mOFC) volume varied significantly as a function of age, as did the correlation between reactive aggression and mOFC surface area. These associations became more positive with age. There were no significant findings for proactive/total aggression. Results are interpreted considering the potential for delayed cortical maturation in youths with high CU traits/aggression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others' distress. This suggests that psychopathic ...traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self has not been previously assessed.
Method
We used whole‐brain functional magnetic resonance imaging to measure neural activation in 14 adolescents with oppositional defiant disorder or conduct disorder and psychopathic traits, as well as 21 healthy controls matched on age, gender, and intelligence. Activation in structures associated with empathic pain perception was assessed as adolescents viewed photographs of pain‐inducing injuries. Adolescents imagined either that the body in each photograph was their own or that it belonged to another person. Behavioral and neuroimaging data were analyzed using random‐effects analysis of variance.
Results
Youths with psychopathic traits showed reduced activity within regions associated with empathic pain as the depicted pain increased. These regions included rostral anterior cingulate cortex, ventral striatum (putamen), and amygdala. Reductions in amygdala activity particularly occurred when the injury was perceived as occurring to another. Empathic pain responses within both amygdala and rostral anterior cingulate cortex were negatively correlated with the severity of psychopathic traits as indexed by PCL:YV scores.
Conclusions
Youths with psychopathic traits show less responsiveness in regions implicated in the affective response to another's pain as the perceived intensity of this pain increases. Moreover, this reduced responsiveness appears to predict symptom severity.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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