Molecular evolution of driver mutations in cancer with microsatellite instability and their impact on tumor progression: Implications for precision medicine in patients with UCEC.

Cancer development is driven by genetic alterations, particularly cancer driver mutations (CDMs), which are associated with aggressive phenotypes and shorter survival. In contrast, higher mutation loads caused by microsatellite instability (MSI) or mismatch repair deficiency (MMRd) can induce anti-cancer immunity, leading to tumor shrinkage and improved responses to immune checkpoint inhibitor (ICI) therapies. However, understanding how CDMs and MSI/MMRd influence cancer evolution remains limited.

The vitamin D hormone, 1,25(OH)D, regulates fibroblast growth factor 23 (FGF23) production in human skin cells.

The bone hormone fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and the enzymatic production of active vitamin D [1,25(OH)D]. Therefore, FGF23 production in bone cells is closely regulated by 1,25(OH)D acting via the vitamin D receptor (VDR). Skin cells can produce hydroxyvitamin D metabolites from its precursor D made through ultraviolet B light exposure.

Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts.

We investigated multiple signaling pathways activated by CYP11A1-derived vitamin D3 hydroxymetabolites in human skin fibroblasts by assessing the actions of these molecules on their cognate receptors and by investigating the role of CYP27B1 in their biological activities. The actions of 20(OH)D3, 20,23(OH)D3, 1,20(OH)D3 and 1,20,23(OH)D3 were compared to those of classical 1,25(OH)D3. This was undertaken using wild type (WT) fibroblasts, as well as cells with , , or CYP27B1 genes knocked down with siRNA.

Regorafenib Promotes Antitumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma.

Purpose: Immune checkpoint blockade (ICB) therapy induces durable tumor regressions in a minority of patients with cancer. In this study, we aimed to identify kinase inhibitors that were capable of increasing the antimelanoma immunity.

Experimental Design: Flow cytometry-based screening was performed to identify kinase inhibitors that can block the IFNγ-induced PD-L1 expression in melanoma cells.

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.

Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties.

CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation.

Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy.

Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2).

Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level.

Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway.

Purpose: Altered cellular metabolism has received increased attention as an important hallmark of cancer. Activation of FASN has been found to be involved in many human tumors. Despite extensive research in FASN function on cancer, the underlying mechanism is not entirely understood yet.

Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells.

The purpose of this study was to determine the potential benefits of combination therapy using dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with nontoxic concentration of bortezomib (BTZ) and gambogic acid (GA) on multiple myeloma (MM) RPMI-8226 cells and possible underlying mechanisms. The effects of BTZ-GA-loaded MNP-Fe3O4 (BTZ-GA/MNPs) on cell proliferation were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,4,-diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM).

Anticancer and multidrug-resistance reversing potential of traditional medicinal plants and their bioactive compounds in leukemia cell lines.

Multidrug resistance remains a serious clinical problem in the successful therapy of malignant diseases. It occurs in cultured tumor cell lines, as well as in human cancers. Therefore, it is critical to develop novel anticancer drugs with multidrug-resistance modulating potential to increase the survival rate of leukemia patients.

Hepatoprotective effect of Rhodiola imbricata rhizome against paracetamol-induced liver toxicity in rats.

Rhodiola imbricata is a perennial herb of the family Crassulaceae, which has significant traditional usage as medicine and is also known to biosynthesize phytochemicals such as flavonoids, coumarins and phenyl glycosides. The present investigation was aimed to estimate the hepatoprotective activity of R. imbricata rhizome acetone extract against paracetamol (2 g/kg) induced liver toxicity.

Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells.

Objective: To investigate the in vitro antioxidant and antiproliferative activity of rhizome extracts of Rhodiola imbricata (R. imbricata) in HT-29 human colon cancer cell line.

Methods: The successively extracted rhizome of R.