Harnessing nanoparticles to improve toxicity after head and neck radiation.

This article reports the evaluation of cerium oxide (CeO(2)) nanoparticles' ability to decrease xerostomia and radiation-induced dermatitis in mice after head and neck radiation. Mice were irradiated using an IC160 x-ray system. Two cohorts were included: (A) No-radiation and (B) 30 Gy/6 fractions, and were randomized into three groups: (1) saline, (2) 15 nM CeO(2) and (3) 15 µM CeO(2). Stimulated salivary flow and radiation-induced dermatitis were evaluated post radiation. Stimulated sialometry demonstrated improved salivary production in all CeO(2) groups in comparison with controls (flow: 204 vs. 115 µL/10 minutes, P = 0.0002). One week post radiation, G-III dermatitis decreased in the 15 µM group in comparison with controls (10% versus 100% incidence, respectively). There was decreased skin hyperpigmentation at 12 weeks in the 15-µM group in comparison with 15-nM and non-CeO(2) groups (50%, 70%, and 90% G-II, respectively). This study suggests that CeO(2) may be radioprotective for salivary production and reduces G-III dermatitis and skin hyperpigmentation incidence. CeO(2) as radioprotectant may be a feasible concept during radiotherapy. FROM THE CLINICAL EDITOR: This study demonstrates in a mouse model that cerium oxide (CeO(2)) nanoparticles may provide an important mechanism in preventing radiation induced xerostomia, a common complication of head and neck radiation treatments.

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice.

The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease.

Phosphate ester hydrolysis of biologically relevant molecules by cerium oxide nanoparticles.

In an effort to characterize the interaction of cerium oxide nanoparticles (CNPs) in biological systems, we explored the reactivity of CNPs with the phosphate ester bonds of p-nitrophenylphosphate (pNPP), ATP, o-phospho-l-tyrosine, and DNA. The activity of the bond cleavage for pNPP at pH 7 is calculated to be 0.860 ± 0.010 nmol p-nitrophenol/min/µg CNPs. Interestingly, when CNPs bind to plasmid DNA, no cleavage products are detected. While cerium(IV) complexes generally exhibit the ability to break phosphorus-oxygen bonds, the reactions we report appear to be dependent on the availability of cerium(III) sites, not cerium(IV) sites. We investigated the dephosphorylation mechanism from the first principles and find the reaction proceeds through inversion of the phosphate group similar to an S(N)2 mechanism. The ability of CNPs to interact with phosphate ester bonds of biologically relevant molecules has important implications for their use as potential therapeutics.

Practical and cost-effective model to build and sustain a cardio-oncology program.

BACKGROUND: Cardio-Oncology (CO) is a new subspecialty that thrives mostly in large academic quaternary centers. This study describes how to establish a successful cardio-oncology program, with limited resources, in order to effectively manage the unique care required by this patient population. METHODS: Clinical data was collected from 25 consecutive months. There were four foundational elements to establish a CO program: 1. Clinical program: integrating staff and resources from the Heart and Vascular, and Cancer Centers; 2. Education Program: establishing a platform to educate/advocate with respect to CO; 3. Engagement with professional societies: active engagement allowed for the successful establishment of the proposed CO program; and 4. Research program: establishing data collection modalities/cooperation with other institutions. RESULTS: 474 consecutive patients were treated by our CO program during the first 25 months of operation. Clinical data, information about cancer treatment, cardiovascular co morbidities, cardiac testing and impact of CO management are reported. CONCLUSIONS: A successful CO program can be established utilizing existing resources without the need for significant additional assets. Integration with professional societies, advocacy, education and research, provide a platform for learning and growth. This model improves access to care and can be reproduced in a variety of settings.