Biodistribution and toxic potential of silver nanoparticles when introduced to the female rat reproductive tract.

The prevalence of ionic silver and silver nanomaterials in hygiene products has been increasing due to their antimicrobial activity. While numerous studies have examined the effects of nanosilver in laboratory settings, there is a limited understanding of its impact on reproductive tissues, as well as its biodistribution and toxicity upon intra-vaginal exposure. If ionic or nanosilver enters adjacent and internal tissues via intra-vaginal exposure, the overuse of hygiene products containing silver may potentially threaten woman's health.

Effect of titanium dioxide nanoparticles on DNA methylation in multiple human cell lines.

Nanoscale titanium dioxide (TiO) is manufactured in wide scale, with a range of applications in consumer products. Significant toxicity of TiO nanoparticles has, however, been recognized, suggesting considerable risk to human health. To evaluate fully their toxicity, assessment of the epigenetic action of these nanoparticles is critical.

Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding.

Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry.

Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. CTCs are the source of metastasis in distant organs that are responsible for the majority of cancer-related deaths. Here we demonstrate the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs released from the primary tumor with a non-invasive real-time in vivo flow cytometry system.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.

Purpose: Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials.

Methods And Materials: The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models.

Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor Vascular Hypoxia.

Developed and tested for many years, a variety of tumor hypoxia detection methods have been inconsistent in their ability to predict treatment outcomes or monitor treatment efficacy, limiting their present prognostic capability. These variable results might stem from the fact that these approaches are based on inherently wide-ranging global tumor oxygenation levels based on uncertain influences of necrotic regions present in most solid tumors. Here, we have developed a novel non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia (vascular hypoxia) has been implicated as a key driver of malignant progression, therapy resistance and metastasis.

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery.

Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).

Methods And Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo--in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods.

Hyperthermia-enhanced indocyanine green delivery for laser-induced thermal ablation of carcinomas.

Purpose: Intravenous administration of indocyanine green (ICG) dye can effectively convert near-infrared (NIR) laser light into heat and enhance thermal injury of blood vessels; however, there is no selective uptake of ICG by the tumour compared to the other tissues, which impacts the therapeutic ratio of this strategy unless uptake can be selectively increased in tumour tissue. Here we investigated the use of local hyperthermia prior to intravenous ICG administration to enhance ICG uptake in tumour tissue, thereby enhancing laser thermal ablation of solid tumours.

Methods: Murine SCK breast or SCCVII head and neck tumours were treated with a 755-nm laser light either alone or with prior intravenous administration of 4 mg/kg ICG and/or local tumour hyperthermia at 42.

Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy.

Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors.

Radiation-induced galectin-1 by endothelial cells: a promising molecular target for preferential drug delivery to the tumor vasculature.

The present study reports on a new strategy for selective, radiation therapy-amplified drug delivery using an antiangiogenic 33-a.a., tumor vasculature-targeting ligand, anginex, to improve the therapeutic ratio for strategies developed against solid tumors.

Microbeam radiation therapy alters vascular architecture and tumor oxygenation and is enhanced by a galectin-1 targeted anti-angiogenic peptide.

In this study, we sought to determine the therapeutic potential of variably sized (50 μm or 500 μm wide, 14 mm tall) parallel microbeam radiation therapy (MRT) alone and in combination with a novel anti-angiogenic peptide, anginex, in mouse mammary carcinomas (4T1)--a moderately hypoxic and radioresistant tumor with propensity to metastasize. The fraction of total tumor volume that was directly irradiated was approximately 25% in each case, but the distance between segments irradiated by the planar microbeams (width of valley dose region) varied by an order of magnitude from 150-1500 μm corresponding to 200 μm and 2000 μm center-to-center inter-microbeam distances, respectively. We found that MRT administered in 50 μm beams at 150 Gy was most effective in delaying tumor growth.

Conductive thermal ablation of 4T1 murine breast carcinoma reduces severe hypoxia in surviving tumour.

Purpose: The purpose of this study was to quantify hypoxia changes in viable tumour volumes after thermal ablation of a murine breast carcinoma.

Methods: Murine breast 4T1 tumours were grown in the rear leg of BALB/c mice to an average diameter of 10-12 mm. Tumours were treated with conductive interstitial thermal therapy (CITT) at a peak temperature of 80-90°C for 10 min.

Vascular disrupting agent arsenic trioxide enhances thermoradiotherapy of solid tumors.

Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation followed by ATO administration and local 42.

Tumor-Endothelial Cell Three-dimensional Spheroids: New Aspects to Enhance Radiation and Drug Therapeutics.

Classic cancer research for several decades has focused on understanding the biology of tumor cells in vitro. However, extending these findings to in vivo settings has been impeded owing to limited insights on the impact of microenvironment on tumor cells. We hypothesized that tumor cell biology and treatment response would be more informative when done in the presence of stromal components, like endothelial cells, which exist in the tumor microenvironment.

Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent.

The effects of ionizing radiation, with or without the anti-angiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice.

Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC).

Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.