Assessing toxicity of amorphous nanoplastics in airway- and lung epithelial cells using air-liquid interface models.

Background: Inhalation is one of the main exposure routes to nanoplastics. Knowledge of the toxicological impact of nanoplastics on the airway- and lung epithelium is limited and almost exclusively based on submerged in vitro models using spherical polystyrene (PS) particles.

Methods: Mono-cultures and advanced (co-)cultures of human bronchial- and alveolar epithelial cells, all air-liquid interface (ALI) cultures, were exposed to nanoplastics and reference nanoparticles.

Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer.

Background: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production.

Methods: We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively.

S(+)-ibuprofen destabilizes MYC/MYCN and AKT, increases p53 expression, and induces unfolded protein response and favorable phenotype in neuroblastoma cell lines.

Neuroblastoma is a common pediatric solid tumor that exhibits a striking clinical bipolarity: favorable and unfavorable. The survival rate of children with unfavorable neuroblastoma remains low among all childhood cancers. MYCN and MYC play a crucial role in determining the malignancy of unfavorable neuroblastomas, whereas high-level expression of the favorable neuroblastoma genes is associated with a good disease outcome and confers growth suppression of neuroblastoma cells.

The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis.

Objective: To test if estrogen promotes carcinogenesis in vitro and in a genetic mouse model of ovarian cancer and whether its effects can be inhibited by a novel selective estrogen receptor modulator (SERM), bazedoxifene.

Methods: Bazedoxifene was synthesized and it was confirmed that the drug abrogated the uterine stimulatory effect of 17β-estradiol in mice. To determine if hormones alter tumorigenesis in vivo LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with vehicle control, 17β-estradiol or bazedoxifene.

Targeting the urokinase plasminogen activator receptor inhibits ovarian cancer metastasis.

Purpose: To understand the functional and preclinical efficacy of targeting the urokinase plasminogen activator receptor (u-PAR) in ovarian cancer.

Experimental Design: Expression of u-PAR was studied in 162 epithelial ovarian cancers, including 77 pairs of corresponding primary and metastatic tumors. The effect of an antibody against u-PAR (ATN-658) on proliferation, adhesion, invasion, apoptosis, and migration was assessed in 3 (SKOV3ip1, HeyA8, and CaOV3) ovarian cancer cell lines.