p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.

Significant efforts have focused on identifying targetable genetic drivers that support the growth of solid tumors and/or increase metastatic ability. During tumor development and progression to metastatic disease, physiological and pharmacological selective pressures influence parallel adaptive strategies within cancer cell sub-populations. Such adaptations allow cancer cells to withstand these stressful microenvironments.

Cell Death Analysis in Cancer Spheroids from a Microfluidic Device.

Microfluidic technology facilitates the generation of 3D spheroids from cancer cells, a more suitable model for preclinical therapeutic studies. This system opens the possibility to test many drugs combination at a low cost. Here we describe the use of microfluidic devices for cytotoxicity evaluation on cancer spheroids for the discovery of drugs that could be used in combination with radiotherapy.

Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip.

STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer.

Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress.

X-ray on chip: Quantifying therapeutic synergies between radiotherapy and anticancer drugs using soft tissue sarcoma tumor spheroids.

Purpose: Radioresistance, tumor microenvironment, and normal tissue toxicity from radiation limit the efficacy of radiotherapy in treating cancers. These challenges can be tackled by the discovery of new radiosensitizing and radioprotecting agents aimed at increasing the therapeutic efficacy of radiotherapy. The goal of this work was to develop a miniaturized microfluidic platform for the discovery of drugs that could be used in combination with radiotherapy.

Apolipoprotein D.

ApoD is a 25 to 30 kDa glycosylated protein, member of the lipocalin superfamily. As a transporter of several small hydrophobic molecules, its known biological functions are mostly associated to lipid metabolism and neuroprotection. ApoD is a multi-ligand, multi-function protein that is involved lipid trafficking, food intake, inflammation, antioxidative response and development and in different types of cancers.

Interplay between ShcA Signaling and PGC-1α Triggers Targetable Metabolic Vulnerabilities in Breast Cancer.

The ShcA adaptor protein transduces oncogenic signals downstream of receptor tyrosine kinases. We show here that breast tumors engage the ShcA pathway to increase their metabolism. ShcA signaling enhanced glucose catabolism through glycolysis and oxidative phosphorylation, rendering breast cancer cells critically dependent on glucose.

Apolipoprotein D deficiency is associated to high bone turnover, low bone mass and impaired osteoblastic function in aged female mice.

Background: Apolipoprotein D (ApoD) is a member of the lipocalin family known to transport small hydrophobic ligands. A major site of ApoD expression in mice is the central nervous system where evidence suggests that it plays a protective role. Gene expression of ApoD was reported in bone-forming osteoblasts but its impact on bone metabolism remains undocumented.

Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice.

Excitotoxicity due to the excessive activation of glutamatergic receptors leads to neuronal dysfunction and death. Excitotoxicity has been implicated in the pathogenesis of a myriad of neurodegenerative diseases with distinct etiologies such as Alzheimer's and Parkinson's. Numerous studies link apolipoprotein D (apoD), a secreted glycoprotein highly expressed in the central nervous system (CNS), to maintain and protect neurons in various mouse models of acute stress and neurodegeneration.

Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake.

Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice.

Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.

Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration.