ABSTRACT
OBJECTIVE: To compare the effect of intravenous (i/v) and subcutaneous (s/c) infusion of syngeneic dendritic cells (DC) loaded or unloaded with lyzate of tumor cells (LTC) on apoptosis and proliferation of thymic and splenic cells in CBA mice with sarcoma 37 (S 37). METHODS: Experiments were carried out on CBA mice bearing transplanted ascitic form of S 37. DC loaded and unloaded with LTC were infused i/v and s/c (2 x 10(5) per animal) every 4 days (3 injections in total). Apoptosis and proliferation of thymic and splenic cells were evaluated using flow cytofluorimetry. RESULTS: It has been found that tumor development is accompanied by altered apoptosis and proliferation level in thymus and spleen. I/v infusion of syngeneic DC loaded and unloaded with LTC rendered the normalizing effect on the state of thymus in spleen in tumor-bearing animals. In the case of s/c infusion such effect of DC is less expressed. The use of DC, loaded with LTC irrespectively of the way of administration renders more durable effect on the functional state of these cells than the use of unloaded DC. CONCLUSION: Injection of syngeneic DC both loaded or unloaded with LTC renders a normalizing effect on the state of organs of immune system in tumor-bearing CBA mice.
Subject(s)
Dendritic Cells , Sarcoma/immunology , Spleen/cytology , Thymus Gland/cytology , Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Infusions, Intravenous , Injections, Subcutaneous , Mice , Mice, Inbred CBA , Neoplasms, Experimental , Sarcoma/pathology , Spleen/immunology , Thymus Gland/immunologyABSTRACT
Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm2. The lethal dose LD50 values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37 degrees C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.
Subject(s)
Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Doxorubicin/pharmacology , Nanostructures/chemistry , Algorithms , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Drug Delivery Systems/methods , Electromagnetic Fields , Electron Spin Resonance Spectroscopy , Fractals , Free Radicals/chemistry , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Microscopy, Electron, Scanning , Nanostructures/ultrastructure , Particle Size , PowdersABSTRACT
AIM: To study in vitro influence of mechanochemically activated (MA) doxorubicin (DOXO) and electromagnetic irradiation (EMI) on human lung carcinoma A-549 cells. METHODS: Solid state DOXO was MA by input energy 20 W/g during 5 min. Tumor cells were exposed to 40 MHz EMI with power density 2 W/cm(2) at temperature 37 degrees C. RESULTS: Particles of MA DOXO have sizes 10 time smaller than officinal DOXO, high performance liquid chromatography analysis showed that parameters of officinal and MA DOXO were quantitatively equal. Mechanochemical activation initiated in the drug formation of free radicals with g = 2.005, g = 2.003 and g = 1.97. LD(50) values of MA DOXO were 5 times lower than that of officinal drug. Cell survival decreased in the following way after effects EMI --> officinal DOXO --> MA DOXO --> officinal DOXO + EMI --> MA DOXO + EMI. CONCLUSION: Treatment by MA DOXO and drug with EMI at 37 degrees C showed better targeting of drug in human lung carcinoma A-549 cells outcomes than officinal DOXO.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/pharmacokinetics , Carcinoma/pathology , Doxorubicin/pharmacology , Doxorubicin/pharmacokinetics , Electromagnetic Fields , Lung Neoplasms/pathology , Drug Delivery Systems , Friction , Humans , Particle Size , Temperature , Tumor Cells, CulturedABSTRACT
Disorders in the immune system manifesting in decreased weight and cellularity of lymphoid organs, decreased count of large granular lymphocytes, suppression of the immune response and metabolic activity of macrophages were observed in experimental animals 1-6 months after thyroidectomy. The intensity of these disorders depends on the period elapsed after the surgery. These disorders can result from not only changes in the levels of the pituitary-thyroid hormones, but also disturbances in the endocrine function of the thymus in thyroidectomized animals.
