FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.

Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1- and Bard1-mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance.

Selective effects of estradiol on human corneal endothelial cells.

In Fuchs endothelial corneal dystrophy (FECD), mitochondrial and oxidative stresses in corneal endothelial cells (HCEnCs) contribute to cell demise and disease progression. FECD is more common in women than men, but the basis for this observation is poorly understood. To understand the sex disparity in FECD prevalence, we studied the effects of the sex hormone 17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of HCEnCs grown under physiologic ([O]) and hyperoxic ([O]) conditions.

Selective effects of estradiol on human corneal endothelial cells.

Fuchs endothelial corneal dystrophy (FECD) results from genetic and environmental factors triggering mitochondrial and oxidative stress in corneal endothelial cells (CEnCs) leading to CEnC death and corneal opacification. FECD is more common in women than men, but the basis for this observation is unknown. Because FECD is commonly diagnosed around the time of the menopausal transition in women when estrogen levels decrease precipitously, we studied the effects of the potent estrogen,17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of human CEnCs (HCEnCs) under conditions of physiologic 2.

Targeting S100A9-ALDH1A1-Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer.

Unlabelled: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood.

Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing.

The hedgehog (Hh) signalling pathway regulates normal development and cell proliferation in metazoan organisms, but its aberrant activation can promote tumorigenesis and progression of a variety of aggressive human cancers including skin cancer. Despite its importance, little is known about its role in photoageing, a type of UV-induced skin lesions. In this study, we investigated the involvement of Hh signalling in the photoageing process as well as the use of an Hh-regulating alkaloid compound as a novel therapeutic drug to regulate photoageing in keratinocytes.

Screening of soy protein-derived hypotriglyceridemic di-peptides in vitro and in vivo.

Background: Soy protein and soy peptides have attracted considerable attention because of their potentially beneficial biological properties, including antihypertensive, anticarcinogenic, and hypolipidemic effects. Although soy protein isolate contains several bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear which peptide sequences are responsible for the triglyceride (TG)-lowering effects. In the present study, we investigated the effects of soy protein-derived peptides on lipid metabolism, especially TG metabolism, in HepG2 cells and obese Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells.

Background: Higher concentrations of serum lipids and apolipoprotein B100 (apoB) are major individual risk factors of atherosclerosis and coronary heart disease. Therefore ameliorative effects of food components against the diseases are being paid attention in the affluent countries. The present study was undertaken to investigate the effect of taurine on apoB secretion and lipid metabolism in human liver model HepG2 cells.

The 9cis,11trans,13cis isomer of conjugated linolenic acid reduces apolipoprotein B100 secretion and triacylglycerol synthesis in HepG2 cells.

The physiological effects of 9cis,11trans,13cis-conjugated linolenic acid (9c,11t,13c-CLNA), one of the CLNA isomers, were studied in human hepatoma HepG2 cells. 9c,11t,13c-CLNA significantly decreased apolipoprotein B100 secretion compared with alpha-linolenic acid (alpha-LNA). The uptake of (14)C-oleate into newly synthesized cellular triacylglycerol was also decreased by 9c,11t,13c-CLNA more than by alpha-LNA treatment.

Cycloalliin, a cyclic sulfur imino acid, reduces serum triacylglycerol in rats.

Allium species such as onions and garlic are used as foodstuff, condiment, flavoring, and folk medicine. Onions may decrease hyperlipidemia and improve atherosclerosis. However, the ingredients in onion that are responsible for this phenomenon are not known.

S-propyl cysteine reduces the secretion of apolipoprotein B100 and triacylglycerol by HepG2 cells.

A number of sulfur-containing amino acids and peptides are found in allium plants such as onion and garlic that have physiologic functions. In HepG2 cells, S-propyl cysteine decreased the secretion of apolipoprotein B100. The compound reduced the secretion of newly synthesized triacylglycerol and cholesterols from radiolabeled acetate.