Metabolic features of tumor-derived extracellular vesicles: challenges and opportunities.

Tumor-derived extracellular vesicles (TDEVs) play crucial roles in intercellular communication both in the local tumor microenvironment and systemically, facilitating tumor progression and metastatic spread. They carry a variety of molecules with bioactive properties, such as nucleic acids, proteins and metabolites, that trigger different signaling processes in receptor cells and induce, among other downstream effects, metabolic reprogramming. Interestingly, the cargo of TDEVs also reflects the metabolic status of the producing cells in a time- and context-dependent manner, providing information on the functionality and state of those cells.

[A panel model of the relationships between loneliness and depression in older adults].

Antecedents And Objective: The declining birth rate and increasing life expectancy have led to an aging population, causing challenges at the economic, social and healthcare levels. Ensuring and maintaining high levels of well-being and mental health in older adults is crucial for successful aging. Given that previous literature indicates that perceived loneliness and depressive symptoms constitute significant obstacles to their quality of life, the aim of this study is to examine how perceived loneliness and depression intertwined in community-dwelling older adults over time.

Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells.

Background: We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression.

Methods & Results: Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature.

Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour.

Structural Validity and Internal Consistency of the Adolescents and Children Risk of Abuse and Maltreatment Parental Scale (ACRAM-PS).

There is a clear need for developing a comprehensive, unbiased, and psychometrically sound tool to assess child maltreatment. The aim of this study is to examine the structural validity, internal consistency, and convergent validity of a newly developed child maltreatment assessment instrument. A total of 286 professionals of the child protection system participated in the study, completing a total of 645 cases of children and adolescents.

Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression.

Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.

Pharmacological targeting of the receptor ALK inhibits tumorigenicity and overcomes chemoresistance in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease characterized by its metastatic potential and chemoresistance. These traits are partially attributable to the highly tumorigenic pancreatic cancer stem cells (PaCSCs). Interestingly, these cells show unique features in order to sustain their identity and functionality, some of them amenable for therapeutic intervention.

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs.

Metabolic determinants of stemness in medulloblastoma.

Medulloblastomas (MBs) are the most prevalent brain tumours in children. They are classified as grade IV, the highest in malignancy, with about 30% metastatic tumours at the time of diagnosis. Cancer stem cells (CSCs) are a small subset of tumour cells that can initiate and support tumour growth.

Protein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3.

Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease.

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma.

Objective: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.

Design: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, ; ; mice (KPC) and the ; mice (KC) were crossed with allele floxed mice ( ) or conditional overexpressing mice (R26 ) to generate KPCL2 or KCL2 and KPCL2 or KCL2 mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.

Durable Response to Vemurafenib and Cobimetinib for the Treatment of BRAF-Mutated Metastatic Melanoma in Routine Clinical Practice.

Background: The combination of and inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings.

Patients And Methods: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019.

Measurement Invariance of the Brief Resilient Coping Scale (BRCS) in Peruvian and Spanish Older Adults.

Although the Brief Resilient Coping Scale (BRCS) has been validated in some European and American countries, there are no studies that evaluate its factorial invariance among different nations. In this sense, the objective of the study is to evaluate the factorial invariance of the BRCS in samples of older adults in Peru and Spain, using multigroup Confirmatory Factor Analysis. 236 older adults from Peru participated (Mean age = 72.

Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer.

Previously regarded as simple fat storage particles, new evidence suggests that lipid droplets (LDs) are dynamic and functional organelles involved in key cellular processes such as membrane biosynthesis, lipid metabolism, cell signalling and inflammation. Indeed, an increased LD content is one of the most apparent features resulting from lipid metabolism reprogramming necessary to support the basic functions of cancer cells. LDs have been associated to different cellular processes involved in cancer progression and aggressiveness, such as tumorigenicity, invasion and metastasis, as well as chemoresistance.

Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.

Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination.

Quality of Life in European Older Adults of SHARE Wave 7: Comparing the Old and the Oldest-Old.

CASP-12 (Control, Autonomy, Self-realization, and Pleasure scale) is one of the most common internationally used measures for quality of life in older adults, although its structure is not clearly established. Current research aims to test the factor structure of the CASP-12, so as to provide evidence on reliability and external validity, and to test for measurement invariance across age groups. Data from 61,355 Europeans (≥60 years old) from the Survey of Health, Ageing and Retirement in Europe wave 7 were used.

Erratum: Hindi, N., et al. Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center. 2020, , 3740.

The authors noticed that content of "Conflicts of Interest" in the original version [...

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration.

(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by β-III spectrin () mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel.

Inhibition of Mitochondrial Dynamics Preferentially Targets Pancreatic Cancer Cells with Enhanced Tumorigenic and Invasive Potential.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, partly due to its intrinsic aggressiveness, metastatic potential, and chemoresistance of the contained cancer stem cells (CSCs). Pancreatic CSCs strongly rely on mitochondrial metabolism to maintain their stemness, therefore representing a putative target for their elimination. Since mitochondrial homeostasis depends on the tightly controlled balance between fusion and fission processes, namely mitochondrial dynamics, we aim to study this mechanism in the context of stemness.

Molecular and Metabolic Subtypes Correspondence for Pancreatic Ductal Adenocarcinoma Classification.

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis.

Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center.

Symptomatic control and tumoral shrinkage is an unmet need in advanced soft-tissue sarcoma (STS) patients beyond first-line. The combination of trabectedin and radiotherapy showed activity in a recently reported clinical trial in this setting. This retrospective series aims to analyze our experience with the same regimen in the real-life setting.