Laser irradiation of ferrous particles for hyperthermia as cancer therapy, a theoretical study.

Our recent in vivo animal studies showed the feasibility of using micron sized iron particles to induce physical damage to breast cancer tumors and thereby triggering a localized immune response to help fight the cancer. Combining a hyperthermic treatment with this ongoing study may enhance the immune response. As a result, a novel treatment of inducing hyperthermia using iron particles excited by a continuous wave near-infrared laser was analyzed. In this theoretical study, Mie scattering calculations were first conducted to determine the absorption and scattering efficiencies of the suspended drug coated particles. The resulting heat transfer between the particles and the surrounding tumor and the healthy tissue was modeled using Pennes' Bioheat equation. Predicted temperature changes were satisfactory for inducing hyperthermia (42(∘)C), thermally triggering drug release, and even thermal ablation (55(∘)C).

Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF) consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+)T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

Interactions of airflow oscillation, tracheal inclination, and mucus elasticity significantly improve simulated cough clearance.

BACKGROUND: Viscoelastic properties of simulated mucus, angle of tracheal inclination (theta), and high-frequency airflow oscillations on median displacement of simulated mucus during simulated cough were investigated in this study. METHODS: Mucus simulants with viscoelastic properties similar to healthy individuals and patients with COPD were prepared using locust bean gum (LBG)-water solution (0.38 g LBG in 100 mL water) cross-linked with 3-mL and 12-mL borax-water solution (0.02 M), respectively. Aliquots of 0.3 mL of simulants were placed on a dry Plexiglas insert inside a D-shaped clear Plexiglas tracheal model. Movement of aliquots of mucus simulants was measured during cough of 0.3 s duration. Cough velocities studied (5-30 m/s) are typical of patients with weak expiratory muscles and airway obstruction. Studies were conducted with tracheal model placed horizontally (0 degrees) and at increasing theta (15 degrees, 30 degrees, and 45 degrees), with and without superimposed airflow oscillations during coughs. Effects of different parameters and their interactions on displacements of aliquots were compared using analysis of covariance (n = 849). RESULTS: Significant positive nonlinear associations existed between displacement and cough velocity for both 3-mL and 12-mL simulants (P < .0001). Displacement was greatest for the cohesive 12-mL simulant at all cough velocities. Displacement increased significantly (P < .0001) as theta was increased for both types of simulants. Largest displacements at low cough velocities occurred with 12-mL simulant in the presence of oscillations at 45 degrees angle. CONCLUSIONS: Results support the use of airflow oscillations and sitting upright to facilitate mucus displacement during cough, particularly with thick, elastic mucus found in patients with COPD (P < .0001).

Response of a viscoelastic layer (mucus) to turbulent airflow in a rigid tube.

Basic interaction mechanism between the air flow and viscoelastic mucus layer lining a rigid tube is computationally studied. Linear wave instability theory is applied to the coupled air-mucus system to explore the stability of the interface. Primary velocity profile is taken to be the mean profile of turbulent flow and turbulent fluctuations are neglected. The model predicts that the instability initiates in the form of slow propagating waves on the mucus surface. Onset flow speed at which these waves initiate is very sensitive to mucus viscosity to elasticity ratio at lower range and it approaches to an asymptotic value for higher values. The results indicate that while the wave length increases, wave speed decreases with increasing mucus viscosity to elasticity ratio. Model also predicts that the waves initiate at lower flow velocities for the turbulent case compared to the published laminar case. Turbulent onset flow speed is only 34% Flow is considered to be turbulent during forced expiration and coughing in central and upper airways. Model predicts that this flow behavior tends to favor wave initiation at lower flow rates and may facilitate cough clearance.

Clearance of viscoelastic mucus simulant with airflow in a rectangular channel, an experimental study.

Interaction of mucus simulant with airflow in a rectangular channel is investigated experimentally. Two different viscoelastic gel mucus simulants are prepared by cross linking Borax with Locust Bean Gum (LBG) solution; liquid-like (LM) with lower storage modulus and semi-solid (SM). The rheological difference between LM and SM represent the qualitative change from liquid-like healthy mucus to the one with higher storage modulus found in a person with lung disease. The study concentrates on the effect of viscoelastic layer thickness and rheology on the wave formation and clearance due to its interaction with airflow. The results indicate that the onset air velocity for wave initiation reduces by increasing layer thickness. This effect is more pronounced for SM. Slowly propagating waves initiate at a lower air velocity for LM compared to SM for thinner layer thickness and this behavior reverses for a thicker layer. Although SM clears at a critical air velocity, LM does not show clearance behavior, defined as separation of layer section from rest and movement in the downstream flow direction. This seems to suggest that thicker mucus with higher elastic modulus, similar to the mucus for a person with lung disease, may clear easier with a two-phase air-liquid flow, as in cough.

Interaction of laminar airflow with viscoelastic airway mucus.

Basic wave interaction mechanism between the laminar airflow and viscoelastic layer in a rigid tube is investigated numerically. The purpose is to explore the effect of mucus viscoelasticity on the stability of the coupled airflow-mucus system in pulmonary airways under clinical conditions where the serous layer is absent. The results indicate that the onset flow speed, for the initiation of unstable surface waves, is very sensitive to mucus viscosity and it may be as high as 35 times the elastic case for a very viscous mucus with the same elasticity. While the onset speed and wavelength increases, wave speed decreases with increasing mucus viscosity, reducing from about 40% of the flow speed for elastic mucus to less than 1% for a very viscous mucus. Also, a case study for a patient with chronic bronchitis shows that large amplitude waves may form on the mucus surface during forced expiration.