Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted.

Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet-loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma.

Previously reported CCDC26 risk variant and novel germline variants in GALNT13, AR, and MYO10 associated with familial glioma in Finland.

Predisposing factors underlying familial aggregation of non-syndromic gliomas are still to be uncovered. Whole-exome sequencing was performed in four Finnish families with brain tumors to identify rare predisposing variants. A total of 417 detected exome variants and 102 previously reported glioma-related variants were further genotyped in 19 Finnish families with brain tumors using targeted sequencing.

Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors.

Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness and aberrant but still unresolved epigenetic regulation. To better understand their malignancy, we investigated how AT/RT-specific DNA hypermethylation was associated with gene expression and altered transcription factor binding and how it is linked to upstream regulation. Medulloblastomas, choroid plexus tumors, pluripotent stem cells, and fetal brain were used as references.

Motor dysfunction as a primary symptom predicts poor outcome: multicenter study of glioma symptoms.

Background And Objectives: The objectives of this study were to investigate the prognostic value of primary symptoms and leading symptoms in adult patients with diffuse infiltrating glioma and to provide a clinical perspective for evaluating survival.

Methods: This study included a retrospective cohort from two tertiary university hospitals ( = 604, 2006-2013, Tampere University Hospital and Turku University Hospital) and a prospective cohort ( = 156, 2014-2018, Tampere University Hospital). Preoperative symptoms were divided into primary and leading symptoms.

Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection.

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first.

Early-onset grade 2-3 diffuse gliomas and schwannomas increase the risk of central nervous system tumors among the patients' relatives.

Background: Central nervous system (CNS) tumors are a heterogeneous group of tumors that include several aggressive malignancies with a high mortality rate. This study aimed to evaluate the familial relative risk of CNS tumors in family members of early-onset index cases (probands) in and between diffuse glioma, non-diffuse glioma, meningioma, and other CNS tumors.

Methods: We retrieved tumor data from the Finnish cancer registry and familial relationships data from the population information system.

PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas.

Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing.

Identification of novel Stat6 regulated proteins in IL-4-treated mouse lymphocytes.

Interleukin 4 (IL-4) has an indispensable role in the differentiation of naive T helper (Th) cells toward the Th2 phenotype and induction of B cells to produce the IgE class of Igs. By regulating these two cell types, IL-4 has a pre-eminent role in regulation of allergic inflammation. IL-4-mediated regulation of T and B cell functions is largely transmitted through signal transducer and activator of transcription 6 (Stat6).

An insight into molecular mechanisms of human T helper cell differentiation.

Selective activation of T helper (Th) cell subsets plays an important role in immune response to pathogens as well as in the pathogenesis of human allergy and inflammatory diseases. Th1 cells along with the recently discovered Th17 cells play a role in the pathogenesis of autoimmune diseases. Th2 cytokines lead to series of inflammatory processes characteristic for asthma and other atopic diseases.

Interleukin-4 inhibits caspase-3 by regulating several proteins in the Fas pathway during initial stages of human T helper 2 cell differentiation.

Interleukin-4 (IL-4) is the main cytokine that polarizes activated naïve CD4+ T cells in the T helper 2 (Th2) direction. IL-4 also regulates the subsequent stages of Th2 cell-mediated diseases, such as allergies. We conducted a proteomics study to identify IL-4-induced differences during the initial stages of T helper cell differentiation.

Proteome characterization of human T helper 1 and 2 cells.

T helper (Th) cells can be polarized into two different main subtypes, Th1 and Th2 cells. Their activation is linked to the eradication of different pathogens and to dissimilar immunological dysfunctions, which implies differences also in their protein expression patterns. To identify these differences, CD4(+) T cells were isolated from human cord blood, polarized in vitro to Th1 and Th2 and activated via CD3 and CD28.