The Temozolomide-Doxorubicin paradox in Glioblastoma in vitro-in silico preclinical drug-screening.

Adjuvant Temozolomide is considered the front-line Glioblastoma chemotherapeutic treatment; yet not all patients respond. Latest trends in clinical trials usually refer to Doxorubicin; yet it can lead to severe side-effects if administered in high doses. While Glioblastoma prognosis remains poor, little is known about the combination of the two chemotherapeutics.

Promyelocytic leukemia protein regulates angiogenesis and epithelial-mesenchymal transition to limit metastasis in MDA-MB-231 breast cancer cells.

Promyelocytic leukemia protein (PML) modulates diverse cell functions that contribute to both tumor suppressor and pro-oncogenic effects, depending on the cellular context. We show here that PML knockdown (KD) in MDA-MB-231, but not MCF7, breast cancer cells, prolonged stem-cell-like survival, and increased cell proliferation and migration, which is in line with gene-enrichment results from their RNA sequencing analysis. Of note, increased migration was accompanied by higher levels of the epithelial-mesenchymal transition (EMT) regulator Twist-related protein 2 (TWIST2).

PML Differentially Regulates Growth and Invasion in Brain Cancer.

Glioblastoma is the most malignant brain tumor among adults. Despite multimodality treatment, it remains incurable, mainly because of its extensive heterogeneity and infiltration in the brain parenchyma. Recent evidence indicates dysregulation of the expression of the Promyelocytic Leukemia Protein (PML) in primary Glioblastoma samples.

Promyelocytic leukemia protein (PML) controls breast cancer cell proliferation by modulating Forkhead transcription factors.

The multitasking promyelocytic leukemia (PML) protein was originally recognized as a tumor-suppressive factor, but more recent evidence has implicated PML in tumor cell prosurvival actions and poor patient prognosis in specific cancer settings. Here, we report that inducible PMLIV expression inhibits cell proliferation as well as self-renewal and impairs cell cycle progression of breast cancer cell lines in a reversible manner. Transcriptomic profiling identified a large number of PML-deregulated genes associated with various cell processes.

Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming.

Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors.

DOα⁻β⁺ expression in favor of HLA-DR engagement in exosomes.

The expression of DOβ and not DOα, in addition to the high intracellular DR, low DM levels and absence of surface DR expression in K562 and HL-60 cells introduce alternative regulatory pathways in DR trafficking and consequently the antigen presentation process. The present study attempted to define the naturally occurring DOα negative state and explain the role of DOβ in the intracellular DR accumulation in K562 and HL-60 cells. Despite the absence of DOα, the DOβ chain was detected in the endosomal compartments.

Gene-specific factors determine mitotic expression and bookmarking via alternate regulatory elements.

Transcriptional silencing during mitosis is caused by inactivation of critical transcriptional regulators and/or chromatin condensation. Inheritance of gene expression patterns through cell division involves various bookmarking mechanisms. In this report, we have examined the mitotic and post-mitotic expression of the DRA major histocompatibility class II (MHCII) gene in different cell types.

Gamma interferon-dependent transcriptional memory via relocalization of a gene locus to PML nuclear bodies.

Memory of past cellular responses is an essential adaptation to repeating environmental stimuli. We addressed the question of whether gamma interferon (IFN-gamma)-inducible transcription generates memory that sensitizes cells to a second stimulus. We have found that the major histocompatibility complex class II gene DRA is relocated to promyelocytic leukemia (PML) nuclear bodies upon induction with IFN-gamma, and this topology is maintained long after transcription shut off.

CIITA regulates transcription onset viaSer5-phosphorylation of RNA Pol II.

We describe the temporal order of recruitment of transcription factors, cofactors and basal transcriptional components and the consequent biochemical events that lead to activation of the major histocompatibility class II (MHCII) DRA gene transcription by IFN-gamma. We found that the gene is 'poised' for activation since both the activators and a fraction of the basal transcriptional machinery are pre-assembled at the enhancer and promoter prior to IFN-gamma treatment. The class II transactivator is synthesized following IFN-gamma treatment and it is recruited to the enhanceosome leading to the subsequent recruitment of the CBP and GCN5 coactivators.