Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer.

Background: Limited therapeutic options are available for triple-negative breast cancer (TNBC), emphasizing an urgent need for more effective treatment approaches. The development of strategies by targeting tumor-associated macrophages (TAMs) to stimulate their ability of Programmed Cell Removal (PrCR) provides a promising new immunotherapy for TNBC treatment.

Methods: CD47 is a critical self-protective "don't eat me" signal on multiple human cancers against macrophage immunosurveillance.

Warburg Effect Is a Cancer Immune Evasion Mechanism Against Macrophage Immunosurveillance.

Evasion of immunosurveillance is critical for cancer initiation and development. The expression of "don't eat me" signals protects cancer cells from being phagocytosed by macrophages, and the blockade of such signals demonstrates therapeutic potential by restoring the susceptibility of cancer cells to macrophage-mediated phagocytosis. However, whether additional self-protective mechanisms play a role against macrophage surveillance remains unexplored.

Dysregulation of ion homeostasis by antifungal agents.

Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils.

Vesicular distribution of Secretory Pathway Ca²+-ATPase isoform 1 and a role in manganese detoxification in liver-derived polarized cells.

Manganese is a trace element that is an essential co-factor in many enzymes critical to diverse biological pathways. However, excess Mn(2+) leads to neurotoxicity, with psychiatric and motor dysfunction resembling parkinsonism. The liver is the main organ for Mn(2+) detoxification by excretion into bile.

Mechanism of antifungal activity of terpenoid phenols resembles calcium stress and inhibition of the TOR pathway.

Terpenoid phenols, including carvacrol, are components of oregano and other plant essential oils that exhibit potent antifungal activity against a wide range of pathogens, including Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa. To gain a mechanistic view of the cellular response to terpenoid phenols, we used Saccharomyces cerevisiae as a model organism and monitored temporal changes in metabolic activity, cytosolic and vacuolar pH, and Ca(2+) transients. Using a panel of related compounds, we observed dose-dependent Ca(2+) bursts that correlated with antifungal efficacy.

Store-independent activation of Orai1 by SPCA2 in mammary tumors.

Ca(2+) is an essential and ubiquitous second messenger. Changes in cytosolic Ca(2+) trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca(2+)-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca(2+) levels and tumorigenicity.

Membrane hyperpolarization drives cation influx and fungicidal activity of amiodarone.

Cationic amphipathic drugs, such as amiodarone, interact preferentially with lipid membranes to exert their biological effect. In the yeast Saccharomyces cerevisiae, toxic levels of amiodarone trigger a rapid influx of Ca(2+) that can overwhelm cellular homeostasis and lead to cell death. To better understand the mechanistic basis of antifungal activity, we assessed the effect of the drug on membrane potential.

Fungicidal activity of amiodarone is tightly coupled to calcium influx.

The antiarrhythmic drug amiodarone has microbicidal activity against fungi, bacteria and protozoa. In Saccharomyces cerevisiae, amiodarone triggers an immediate burst of cytosolic Ca2+, followed by cell death markers. Ca2+ transients are a common response to many forms of environmental insults and toxic compounds, including osmotic and pH shock, endoplasmic reticulum stress, and high levels of mating pheromone.

A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension.

Phylogenetic analysis of the cation/proton antiporter superfamily has uncovered a previously unknown clade of genes in metazoan genomes, including two previously uncharacterized human isoforms, NHA1 and NHA2, found in tandem on human chromosome 4. The NHA (sodium hydrogen antiporter) family members share significant sequence similarity with Escherichia coli NhaA, including a conserved double aspartate motif in predicted transmembrane 5. We show that HsNHA2 (Homo sapiens NHA2) resides on the plasma membrane and, in polarized MDCK cells, localizes to the apical domain.

A phenomics approach in yeast links proton and calcium pump function in the Golgi.

The Golgi-localized Ca2+- and Mn2+-transporting ATPase Pmr1 is important for secretory pathway functions. Yeast mutants lacking Pmr1 show growth sensitivity to multiple drugs (amiodarone, wortmannin, sulfometuron methyl, and tunicamycin) and ions (Mn2+ and Ca2+). To find components that function within the same or parallel cellular pathways as Pmr1, we identified genes that shared multiple pmr1 phenotypes.