Autophagy in major human diseases

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders

Prognostic significance and correlation to gene expression profile of EZH2 mutations in diffuse large B‐cell lymphoma (DLBL) in 2 large prospective studies

EZH2, a histone methyl transferase subunit of Polycomb repressor complex 2, is frequently mutated in DLBL. Inhibitors of EZH2 have demonstrated promising responses in early clinical trials. We examined the frequency of EZH2 mutation in 2 large prospective series of DLBL and correlated this to clinical outcomes in relation to other biological features

Differential efficacy of bortezomib in subtypes of diffuse large B‐cell lymphoma (dlbl): a prospective randomised study stratified by transcriptome profiling: remodl‐B

DLBL subtypes identified by patterns of gene expression correspond to germinal center (GCB) or activated (ABC) B‐cells like. The latter demonstrate dysregulation of the NF‐KB pathway. Outcomes of treatment with R‐CHOP are inferior for ABC DLBL in retrospective series. This study investigated whether adding bortezomib (B),a putative NF‐KB inhibitor, can reverse this phenotype

DIFFERENTIAL EFFICACY OF BORTEZOMIB IN SUBTYPES OF DIFFUSE LARGE B-CELL LYMPHOMA (DLBL): a PROSPECTIVE RANDOMISED STUDY STRATIFIED BY TRANSCRIPTOME PROFILING: REMODL-B

Effect of esculetin on HEK293 cancer cells: Effect of different concentrations of esculetin on cell viability using MTT assay in HEK 293 cell line. Data represents the mean ± SD of three independent experiments. (TIF 23 kb

Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV

Although the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known about the potential biological differences between stage I and stage III/IV disease. Using next-generation sequencing and immunohistochemistry, 82 FL nodal stage I cases were analyzed and compared with 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations, and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T cells (P = .02) and STAT6 mutations (false discovery rate [FDR] <0.001) were more frequent in stage I FL. In contrast, programmed cell death protein 1-positive T cells, CD68+/CD163+ macrophages (P < .001), BCL2 translocation (BCL2trl+) (P < .0001), and KMT2D (FDR = 0.003) and CREBBP (FDR = 0.04) mutations were found more frequently in stage III/IV FL. Using clustering, we identified 3 clusters within stage I, and 2 clusters within stage III/IV. The BLC2trl+ stage I cluster was comparable to the BCL2trl+ cluster in stage III/IV. The two BCL2trl- stage I clusters were unique for stage I. One was enriched for CREBBP (95%) and STAT6 (64%) mutations, without BLC6 translocation (BCL6trl), whereas the BCL2trl- stage III/IV cluster contained BCL6trl (64%) with fewer CREBBP (45%) and STAT6 (9%) mutations. The other BCL2trl- stage I cluster was relatively heterogeneous with more copy number aberrations and linker histone mutations. This exploratory study shows that stage I FL is genetically heterogeneous with different underlying oncogenic pathways. Stage I FL BCL2trl- is likely STAT6 driven, whereas BCL2trl- stage III/IV appears to be more BCL6trl driven