Isolating Primary Tumor Cells from the MMTV-PyMT Mouse Model and Their Use in Developing an Orthotopic Mouse Model of Breast Cancer.

To study the effect of the immunologically unimpaired microenvironment on tumor progression as well as the efficacy of therapies requiring a functioning immune system, xenograft models are not suitable due to the use of immunodeficient mice. With orthotopic congenic transplantation of tumor cells into mammary tissue, we gain more control and reproducibility regarding tumor growth, while retaining a functioning immune response. Here, we provide a protocol for isolating primary tumor cells from the MMTV-PyMT mouse model and their use in developing an orthotopic mouse model of breast cancer.

A New Cathepsin D Targeting Drug Delivery System Based on Immunoliposomes Functionalized with Lipidated Pepstatin A.

Cathepsin D is an aspartic protease and one of the most abundant proteases. It is overexpressed in many cancers and plays an important role in tumor development, progression, and metastasis. While it is a physiologically intracellular protein, cathepsin D is secreted into the extracellular matrix under pathological conditions, making it an appealing target for drug delivery systems.

A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD metabolism.

Nicotinamide riboside (NR) is a form of vitamin B and is one of the most studied compounds for the restoration of cellular NAD levels demonstrating clinical potential in many metabolic and age-related disorders. Despite its wide commercial availability as a powerful nutraceutical, our understanding of NR uptake by different cells and tissues is greatly limited by the lack of noninvasive in vivo imaging tools limiting its clinical translation. Here, we report the development and validation of a bioluminescent NR uptake probe (BiNR) for non-invasive longitudinal imaging of NR uptake both in vitro and in vivo.

Theranostic Applications of an Ultra-Sensitive and Magnetic Resonance Contrast Agent Based on Cobalt Ferrite Spinel Nanoparticles.

Nano-dimensional materials have become a focus of multiple clinical applications due to their unique physicochemical properties. Magnetic nanoparticles represent an important class of nanomaterials that are widely studied for use as magnetic resonance (MR) contrast and drug delivery agents, especially as they can be detected and manipulated remotely. Using magnetic cobalt ferrite spinel (MCFS) nanoparticles, this study was aimed at developing a multifunctional drug delivery platform with MRI capability for use in cancer treatment.

Evaluation of novel cathepsin-X inhibitors in vitro and in vivo and their ability to improve cathepsin-B-directed antitumor therapy.

New therapeutic targets that could improve current antitumor therapy and overcome cancer resistance are urgently needed. Promising candidates are lysosomal cysteine cathepsins, proteolytical enzymes involved in various critical steps during cancer progression. Among them, cathepsin X, which acts solely as a carboxypeptidase, has received much attention.

continuous three-dimensional magnetic resonance microscopy: a study of metamorphosis in Carniolan worker honey bees ().

Three-dimensional (3D) magnetic resonance microscopy (MRM) is a modality of magnetic resonance imaging (MRI) optimized for the best resolution. Metamorphosis of the Carniolan worker honey bee () was studied under controlled temperature and humidity conditions from sealed larvae until the emergence of an adult. The 3D images were analyzed by volume rendering and segmentation, enabling the analysis of the body, tracheal system and gastrointestinal tract through the time course of volume changes.

Cysteine cathepsins as therapeutic targets in inflammatory diseases.

: Cysteine cathepsins are involved in the development and progression of numerous inflammation-associated diseases such as cancer, arthritis, bone and immune disorders. Consequently, there is a drive to progress research efforts focused on cathepsin use in diagnostics and as therapeutic targets in disease.: This review discusses the potential of cysteine cathepsins as therapeutic targets in inflammation-associated diseases and recent advances in preclinical and clinical research.

Stefin A-functionalized liposomes as a system for cathepsins S and L-targeted drug delivery.

Proteolytic activity in the tumor microenvironment is one of the key elements supporting tumor development and metastasis. One of the key families of proteases that are overexpressed in various types of cancer and implicated in different stages of tumor progression are cysteine cathepsins. Among them, cathepsins S and L can be secreted into the tumor microenvironment by tumor and/or immune cells, making them promising drug delivery targets.

Bioluminescent-based imaging and quantification of glucose uptake in vivo.

Glucose is a major source of energy for most living organisms, and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited owing to the lack of robust tools. To date, positron-emission tomography imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings.

Crumpled Aluminum Hydroxide Nanostructures as a Microenvironment Dysregulation Agent for Cancer Treatment.

Owing to their unique physicochemical properties, nanomaterials have become a focus of multidisciplinary research efforts including investigations of their interactions with tumor cells and stromal compartment of tumor microenvironment (TME) toward the development of next-generation anticancer therapies. Here, we report that agglomerates of radially assembled Al hydroxide crumpled nanosheets exhibit anticancer activity due to their selective adsorption properties and positive charge. This effect was demonstrated in vitro by decreased proliferation and viability of tumor cells, and further confirmed in two murine cancer models.

A role for stefin B (cystatin B) in inflammation and endotoxemia.

Stefin B (cystatin B) is an endogenous cysteine cathepsin inhibitor, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht-Lundborg disease (EPM1). In this study we demonstrated that stefin B-deficient (StB KO) mice were significantly more sensitive to the lethal LPS-induced sepsis and secreted higher amounts of pro-inflammatory cytokines IL-1β and IL-18 in the serum. We further showed that increased caspase-11 gene expression and better pro-inflammatory caspase-1 and -11 activation determined in StB KO bone marrow-derived macrophages resulted in enhanced IL-1β processing.

Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor.

Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC-NS-629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC-NS-629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment.

Promising approaches in using magnetic nanoparticles in oncology.

The development of new and effective drug delivery systems for cancer treatment represents one of the significant challenges facing biomedical technology in the last decade. Among the different methods of drug delivery, magnetic drug targeting, by enabling specific delivery of chemotherapeutic agents through the use of magnetic nanoparticles and magnetic field gradient, could be a promising approach. Recently, magnetic nanoparticles have attracted additional attention because of their potential as contrast agents for magnetic resonance imaging and heat mediators for cancer therapy.

Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment.

The tumour microenvironment regulates tumour progression and the spread of cancer in the body. Targeting the stromal cells that surround cancer cells could, therefore, improve the effectiveness of existing cancer treatments. Here, we show that magnetic nanoparticle clusters encapsulated inside a liposome can, under the influence of an external magnet, target both the tumour and its microenvironment.