Breast cancer is the most commonly occurring cancer in women worldwide and the second most common cancer overall. The development of new therapies to treat this devastating malignancy is needed urgently. Nanoparticles are one class of nanomaterial with multiple applications in medicine, ranging from their use as drug delivery systems and the promotion of changes in cell morphology to the control of gene transcription. Nanoparticles made of the natural polymer chitosan are easy to produce, have a very low immunogenic profile, and diffuse easily into cells. One hallmark feature of cancer, including breast tumours, is the genome instability caused by defects in the spindle-assembly checkpoint (SAC), the molecular signalling mechanism that ensures the timely and high-fidelity transmission of the genetic material to an offspring. In recent years, the use of nanoparticles to treat cancer cells has gained momentum. This is in part because nanoparticles made of different materials can sensitise cancer cells to chemotherapy and radiotherapy. These advances prompted us to study the potential sensitising effect of chitosan-based nanoparticles on breast cancer cells treated with reversine, which is a small molecule inhibitor of Mps1 and Aurora B that induces premature exit from mitosis, aneuploidy, and cell death, before and after exposure of the cancer cells to X-ray irradiation. Our measurements of metabolic activity as an indicator of cell viability, DNA damage by alkaline comet assay, and immunofluorescence using anti-P-H3 as a mitotic biomarker indicate that chitosan nanoparticles elicit cellular responses that affect mitosis and cell viability and can sensitise breast cancer cells to X-ray radiation (2Gy). We also show that such a sensitisation effect is not caused by direct damage to the DNA by the nanoparticles. Taken together, our data indicates that chitosan nanoparticles have potential application for the treatment of breast cancer as adjunct to radiotherapy.
Ionizing Radiation (IR), especially at high doses, induces cellular senescence in exposed cultures. IR also induces “bystander effects” through signals released from irradiated cells, and these effects include many of the same outcomes observed following direct exposure. Here, we investigate if radiation can cause senescence through a bystander mechanism. Control cultures were exposed directly to 0, 0.1, 2, and 10 Gy. Unirradiated cells were treated with medium from irradiated cultures or with exosomes extracted from irradiated medium. The level of senescence was determined post-treatment (24 h, 15 days, 30 days, and 45 days) by β-galactosidase staining. Media from cultures exposed to all four doses, and exosomes from these cultures, induced significant senescence in recipient cultures. Senescence levels were initially low at the earliest timepoint, and peaked at 15 days, and then decreased with further passaging. These results demonstrate that senescence is inducible through a bystander mechanism. As with other bystander effects, bystander senescence was induced by a low radiation dose. However, unlike other bystander effects, cultures recovered from bystander senescence after repeated passaging. Bystander senescence may be a potentially significant effect of exposure to IR, and may have both beneficial and harmful effects in the context of radiotherapy.
Thalassemia is the world's most common hereditary disease; therefore, more interest has been devoted for the development of the screening procedure of this disease. In beta-thalassemia major, the subject of the current study, impaired biosynthesis of beta-globin leads to accumulation of unpaired alpha-globin chain. The objective of the present study, was to examine many of the biophysical properties of beta-thalassemia major red blood cells (RBCs) and to study the possibility of use of any of them as a preliminary screening tool for beta-thalassemia. The percentage of normal hemolysis, osmotic fragility test, turbidity test, rheological properties, and dielectric properties, were studied in 20 regularly blood transfused thalassemia major patients who were under chelation therapy and their status were compared with those of 10 healthy subjects. There was an increase in the percentage of hemolysis for beta-thalassemia by 114.6% compared to the normal RBCs. The fragility curve for beta-thalassemia RBCs showed a shift toward lower NaCl concentration compared to the normal curve. The average osmotic fragility (H(50): the NaCl concentration producing 50% homolysis) for beta-thalassemia was found to be 3.21 +/- 0.67 g/l, whereas for normal RBCs it was 5.5 +/- 0.31 g/l. The turbidity curve of the beta-thalassemic RBCs showed a shift toward higher detergent concentration of the normal curve, with higher value for the average membrane solubilization (S(50)). The viscosity value of whole blood beta-thalassemia was found to be 3.916 +/- 0.56 cp whereas for normal blood was 2.516 +/- 0.36 cp. The relative permittivity, dielectric loss, and AC conductivity of RBCs decreased significantly compared to normal samples. This could be attributed to the loss of the insulating properties of the membrane and loss of its surface charge of thalassemic RBCs. As can be noticed, several factors showed clear difference between thalassemic and normal blood samples. Some of these parameters could be measured immediately after sample withdrawal and require short time to perform the measurements. This offers the advantages of being effective, low cost, and fast techniques, therefore, we suggest that these techniques could be applied for beta-thalassemia major screening purposes.
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