CCL2-Mediated Stromal Interactions Drive Macrophage Polarization to Increase Breast Tumorigenesis.

CCL2 is an inflammatory cytokine that regulates macrophage activity and is implicated in increased mammographic density and early breast tumorigenesis. The role of CCL2 in mediating stromal interactions that contribute to breast tumorigenesis has yet to be fully elucidated. THP-1-derived macrophages and mammary fibroblasts were co-cultured for 72 h.

Immune Regulation of Mammary Fibroblasts and the Impact of Mammographic Density.

Mammographic density is associated with a 4-6-fold increase in breast cancer risk independent of age and BMI. High mammographic density is characterized by breast tissue with high proportions of stroma comprised of fibroblasts, collagen, and immune cells. This study sought to investigate whether stromal fibroblasts from high mammographic density breast tissue contributes to increased extracellular matrix deposition and pro-tumorigenic signaling.

Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer (IR700Dye) that is activated by near-infrared light irradiation. We previously reported on the use of NIR-PIT with a small protein mimetic, the Affibody molecule (6-7 kDa), instead of a monoclonal antibody. In this study, we investigated a combination of NIR-PIT for HER2-positive breast cancer cells (SK-BR3, MDA-MB361, and JIMT1) with HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate.

Biological Mechanisms and Therapeutic Opportunities in Mammographic Density and Breast Cancer Risk.

Mammographic density is an important risk factor for breast cancer; women with extremely dense breasts have a four to six fold increased risk of breast cancer compared to women with mostly fatty breasts, when matched with age and body mass index. High mammographic density is characterised by high proportions of stroma, containing fibroblasts, collagen and immune cells that suggest a pro-tumour inflammatory microenvironment. However, the biological mechanisms that drive increased mammographic density and the associated increased risk of breast cancer are not yet understood.

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models.

Purpose: Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment.

Plant-derived soybean peroxidase stimulates osteoblast collagen biosynthesis, matrix mineralization, and accelerates bone regeneration in a sheep model.

Bone defects arising from fractures or disease represent a significant problem for surgeons to manage and are a substantial economic burden on the healthcare economy. Recent advances in the development of biomaterial substitutes provides an attractive alternative to the current "gold standard" autologous bone grafting. Despite on-going research, we are yet to identify cost effective biocompatible, osteo-inductive factors that stimulate controlled, accelerated bone regeneration.

Attenuated TGFB signalling in macrophages decreases susceptibility to DMBA-induced mammary cancer in mice.

Background: Transforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates mammary gland development and cancer progression through endocrine, paracrine and autocrine mechanisms. TGFB1 also plays roles in tumour development and progression, and its increased expression is associated with an increased breast cancer risk. Macrophages are key target cells for TGFB1 action, also playing crucial roles in tumourigenesis.

Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle in mice.

Female mice heterozygous for a genetic mutation in transcription factor forkhead box p3 (Foxp3) spontaneously develop mammary cancers; however, the underlying mechanism is not well understood. We hypothesised that increased cancer susceptibility is associated with an underlying perturbation in mammary gland development. The role of Foxp3 in mammary ductal morphogenesis was investigated in heterozygous Foxp3Sf/+ and wildtype Foxp3+/+ mice during puberty and at specific stages of the oestrous cycle.

Near-Infrared Photoimmunotherapy Using a Small Protein Mimetic for HER2-Overexpressing Breast Cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a new and promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer which is activated by near-infrared light irradiation, causing cell death. We investigated NIR-PIT using a small protein mimetic (6-7 kDa), Affibody molecules, instead of a monoclonal antibody for HER2-overexpressing cancer. Because of its small size, the Affibody has rapid clearance, high imaging contrast, and good tumor penetration.

Clodronate-Liposome Mediated Macrophage Depletion Abrogates Multiple Myeloma Tumor Establishment In Vivo.

Multiple myeloma is a fatal plasma cell malignancy that is reliant on the bone marrow microenvironment. The bone marrow is comprised of numerous cells of mesenchymal and hemopoietic origin. Of these, macrophages have been implicated to play a role in myeloma disease progression, angiogenesis, and drug resistance; however, the role of macrophages in myeloma disease establishment remains unknown.

Engineering of Micro- to Nanostructured 3D-Printed Drug-Releasing Titanium Implants for Enhanced Osseointegration and Localized Delivery of Anticancer Drugs.

Primary and secondary bone cancers are major causes of pathological bone fractures which are usually treated through implant fixation and chemotherapy. However, both approaches face many limitations. On one hand, implants may suffer from poor osseointegration, and their rejection results in repeated surgery, patient's suffering, and extensive expenses.

Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma.

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM).

Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics.

pH stimuli responsive drug delivery platforms that can target specific locations along the gastrointestinal tract hold great promise for colorectal cancer therapy. Herein, we present a facile approach to produce microfluidic engineered pH-sensitive magnetic microspherical carriers containing multifunctional therapeutic payloads for synergistic treatment of colorectal cancer. Chemotherapeutics, 5 fluorouracil (5FU) and curcumin (CUR), were chosen due to their synergistic effect for colorectal cancer treatment and prevention.

Evaluation of the combined use of metronomic zoledronic acid and Coriolus versicolor in intratibial breast cancer mouse model.

Ethnopharmacological Relevance: Coriolus versicolor (CV) is a mushroom traditionally used for strengthening the immune system and nowadays used as immunomodulatory adjuvant in anticancer therapy. Breast cancer usually metastasizes to the skeleton, interrupts the normal bone remodeling process and causes osteolytic bone lesions. The aims of the present study were to evaluate its herb-drug interaction with metronomic zoledronate in preventing cancer propagation, metastasis and bone destruction.

In vivo toxicological assessment of electrochemically engineered anodic alumina nanotubes: a study of biodistribution, subcutaneous implantation and intravenous injection.

Electrochemically engineered anodic alumina nanotubes (AANTs) have recently shown good in vitro biocompatibility. However, in vivo toxicological and pathological studies are required to clarify the bio-safety of this novel nanomaterial. Herein, we present a pioneering pilot toxicity study on AANTs in immune-competent murine models (Balb/c mice, 8 weeks).

Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment.

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality.

CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

Background: Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored.

Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells.

Peroxidase enzymes inhibit osteoclast differentiation and bone resorption.

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in abundance by innate immune infiltrates at sites of inflammation and injury. We have discovered new and previously unrecognised roles for heme peroxidases in extracellular matrix biosynthesis, angiogenesis, and bone mineralisation, all of which play an essential role in skeletal integrity. In this study we used in vitro models of osteoclastogenesis to investigate the effects of heme peroxidase enzymes on osteoclast differentiation and bone resorbing activity, pertinent to skeletal development and remodelling.

From The Mine to Cancer Therapy: Natural and Biodegradable Theranostic Silicon Nanocarriers from Diatoms for Sustained Delivery of Chemotherapeutics.

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages.

Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic.

Iron oxide nanowires produced by bacteria (Mariprofundus ferrooxydans) are demonstrated as new multifunctional drug carriers for triggered therapeutics release and cancer hyperthmia applications. Iron oxide nanowires are obtained from biofilm waste in the bore system used to pump saline groundwater into the River Murray, South Australia (Australia) and processed into individual nanowires with extensive magnetic properties. The drug carrier capabilities of these iron oxide nanowires (Bac-FeOxNWs) are assessed by loading anticancer drug (doxorubicin, Dox) followed by measuring its elution under sustained and triggered release conditions using alternating magnetic field (AMF).

Titanium wire implants with nanotube arrays: A study model for localized cancer treatment.

Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach.