Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy.

Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression.

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model.

Background: Systemic drug delivery to the central nervous system is limited by presence of the blood-brain barrier (BBB). Low intensity focused ultrasound (LiFUS) is a non-invasive technique to disrupt the BBB, though there is a lack of understanding of the relationship between LiFUS parameters, such as cavitation dose, time of sonication, microbubble dose, and the time course and magnitude of BBB disruption. Discrepancies in these data arise from experimentation with modified, clinically untranslatable transducers and inconsistent parameters for sonication.

Modulation of the blood-tumor barrier to enhance drug delivery and efficacy for brain metastases.

The blood-brain barrier is the selectively permeable vasculature of the brain vital for maintaining homeostasis and neurological function. Low permeability is beneficial in the presence of toxins and pathogens in the blood. However, in the presence of metastatic brain tumors, it is a challenge for drug delivery.

Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.

In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed.

Nanoparticles as a Tool in Neuro-Oncology Theranostics.

The rapid growth of nanotechnology and the development of novel nanomaterials with unique physicochemical characteristics provides potential for the utility of nanomaterials in theranostics, including neuroimaging, for identifying neurodegenerative changes or central nervous system malignancy. Here we present a systematic and thorough review of the current evidence pertaining to the imaging characteristics of various nanomaterials, their associated toxicity profiles, and mechanisms for enhancing tropism in an effort to demonstrate the utility of nanoparticles as an imaging tool in neuro-oncology. Particular attention is given to carbon-based and metal oxide nanoparticles and their theranostic utility in MRI, CT, photoacoustic imaging, PET imaging, fluorescent and NIR fluorescent imaging, and SPECT imaging.

A Review of Mathematics Determining Solute Uptake at the Blood-Brain Barrier in Normal and Pathological Conditions.

The blood-brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, , is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of for new drug candidates using both intravenous and in situ protocols.