Search

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect. Inclusion criteria regarded children/adolescents diagnosed with cancer on treatment or

IntroductionTask set inhibition supports optimal switching among tasks by actively suppressing the interference from recently executed competing task sets. It is typically studied in cued task-switching paradigms where there is no uncertainty about the task set or rule to prepare for on each trial. While inhibition has been shown to influence the speed and the accuracy of task execution, affecting task set retrieval, preparation, or implementation in conditions of task set switching, it remains uninvestigated whether it also affects rule selection under uncertainty.MethodsWe implemented an ad-hoc four-rule card sorting task and categorized the rules selected by participants after a rule shift according to the recency of their last usage. We included a measure of working memory capacity (WMC) to control for its involvement in the rule selection process.ResultsParticipants exhibited a reduced preference for recently abandoned rules than less recently abandoned ones. Furthermore, we found that such a preference was not associated with WMC.DiscussionThe results suggest that decision-making processes underlying rule inference and selection may be influenced by task-set inhibition, configuring as a conflict adjustment mechanism to the sequential history of rules application.

The extracellular matrix remodeling in the skin results from a delicate balance of synthesis and degradation of matrix components, ensuring tissue homeostasis. These processes are altered during tumor invasion and growth, generating a microenvironment that supports growth, invasion, and metastasis. Apart from the cellular component, the tumor microenvironment is rich in extracellular matrix components and bound factors that provide structure and signals to the tumor and stromal cells. The continuous remodeling in the tissue compartment sustains the developing tumor during the various phases providing matrices and proteolytic enzymes. These are produced by cancer cells and stromal fibroblasts. In addition to fostering tumor growth, the expression of specific extracellular matrix proteins and proteinases supports tumor invasion after the initial therapeutic response. Lately, the expression and structural modification of matrices were also associated with therapeutic resistance. This review will focus on the significant alterations in the extracellular matrix components and the function of metalloproteinases that influence skin cancer progression and support the acquisition of therapeutic resistance.

Cutavirus was previously found in cutaneous melanoma. We detected cutavirus DNA in only 2/185 melanoma biopsies and in 0/52 melanoma metastases from patients in Germany. Viral DNA was localized in the upper epidermal layers. Swab specimens from healthy skin were cutavirus positive for 3.8% (9/237) of immunocompetent and 17.1% (35/205) of HIV-positive men.

Introduction: Task set inhibition supports optimal switching among tasks by actively suppressing the interference from recently executed competing task sets. It is typically studied in cued task-switching paradigms where there is no uncertainty about the task set or rule to prepare for on each trial. While inhibition has been shown to influence the speed and the accuracy of task execution, affecting task set retrieval, preparation, or implementation in conditions of task set switching, it remains uninvestigated whether it also affects rule selection under uncertainty. Methods: We implemented an ad-hoc four-rule card sorting task and categorized the rules selected by participants after a rule shift according to the recency of their last usage. We included a measure of working memory capacity (WMC) to control for its involvement in the rule selection process. Results: Participants exhibited a reduced preference for recently abandoned rules than less recently abandoned ones. Furthermore, we found that such a preference was not associated with WMC. Discussion: The results suggest that decision-making processes underlying rule inference and selection may be influenced by task-set inhibition, configuring as a conflict adjustment mechanism to the sequential history of rules application. [ABSTRACT FROM AUTHOR]

Cutavirus, a novel human protoparvovirus with linear single-stranded DNA, has been detected in fecal samples from children with diarrhea and in cutaneous T-cell lymphomas (CTCL) (1,2). Recently, Mollerup et al. [...]

Netrins are secreted guidance factors that promote axon outgrowth and orientation during nervous system development. Here the authors present structural and biological evidence that netrin-4 is not a guidance cue per se, but rather functions to modulate laminin-laminin interactions.

ADAM9 is a metalloproteinase strongly expressed at the tumor-stroma border by both tumor and stromal cells. We previously showed that the host deletion of ADAM9 leads to enhanced growth of grafted B16F1 melanoma cells by a mechanism mediated by TIMP1 and the TNF-α/sTNFR1 pathway. This study aimed to dissect the structural modifications in the tumor microenvironment due to the stromal expression of ADAM9 during melanoma progression. We performed proteomic analysis of peritumoral areas of ADAM9 deleted mice and identified the altered expression of several matrix proteins. These include decorin, collagen type XIV, fibronectin, and collagen type I. Analysis of these matrices in the matrix producing cells of the dermis, fibroblasts, showed that ADAM9−/− and wild type fibroblasts synthesize and secreted almost comparable amounts of decorin. Conversely, collagen type I expression was moderately, but not significantly, decreased at the transcriptional level, and the protein increased in ADAM9−/− fibroblast mono- and co-cultures with melanoma media. We show here for the first time that ADAM9 can release a collagen fragment. Still, it is not able to degrade collagen type I. However, the deletion of ADAM9 in fibroblasts resulted in reduced MMP-13 and -14 expression that may account for the reduced processing of collagen type I. Altogether, the data show that the ablation of ADAM9 in the host leads to the altered expression of peritumoral extracellular matrix proteins that generate a more favorable environment for melanoma cell growth. These data underscore the suppressive role of stromal expression of ADAM9 in tumor growth and call for a better understanding of how protease activities function in a cellular context for improved targeting.

Secretion of extracellular vesicles (EVs) is a ubiquitous mechanism of intercellular communication based on the exchange of effector molecules, such as growth factors, cytokines, and nucleic acids. Recent studies identified tumor-derived EVs as central players in tumor progression and the establishment of the tumor microenvironment (TME). However, studies on EVs from classical Hodgkin lymphoma (cHL) are limited. The growth of malignant Hodgkin and Reed–Sternberg (HRS) cells depends on the TME, which is actively shaped by a complex interaction of HRS cells and stromal cells, such as fibroblasts and immune cells. HRS cells secrete cytokines and angiogenic factors thus recruiting and inducing the proliferation of surrounding cells to finally deploy an immunosuppressive TME. In this study, we aimed to investigate the role of tumor cell-derived EVs within this complex scenario. We observed that EVs collected from Hodgkin lymphoma (HL) cells were internalized by fibroblasts and triggered their migration capacity. EV-treated fibroblasts were characterized by an inflammatory phenotype and an upregulation of alpha-smooth muscle actin (α-SMA), a marker of cancer-associated fibroblasts. Analysis of the secretome of EV-treated fibroblast revealed an enhanced release of pro-inflammatory cytokines (e.g., IL-1α, IL-6, and TNF-α), growth factors (G-CSF and GM-CSF), and pro-angiogenic factors such as VEGF. These soluble factors are known to promote HL progression. In line, ingenuity pathway analysis identified inflammatory pathways, including TNF-α/NF-κB-signaling, as key factors directing the EV-dependent phenotype changes in fibroblasts. Confirming the in vitro data, we demonstrated that EVs promote α-SMA expression in fibroblasts and the expression of proangiogenic factors using a xenograft HL model. Collectively, we demonstrate that HL EVs alter the phenotype of fibroblasts to support tumor growth, and thus shed light on the role of EVs for the establishment of the tumor-promoting TME in HL.