Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study). Bioluminescence area of the primary tumor significantly decreased on days 21 and 28; the total number of visceral metastases also decreased according to magnetic-resonance imaging data. Resorba monotherapy produced no general toxic effect, the median survival increased to 64 days, and 90-day survival was 33%. Imaging techniques (magnetic-resonance imaging, microtomography, bioluminescent analysis) showed that Resorba delayed the development of the primary tumor (regression of luminescence area on days 21 and 28, regression of standardized bioluminescence intensity on day 28) and significantly reduced the number of visceral metastases in comparison with the control. Combination therapy was less effective than monotherapy with the same medications. Median survival was 55 days, 90-day survival was 13%, but magnetic-resonance imaging and bioluminescence analysis after combination therapy also showed delayed growth of the primary tumor and reduced number of visceral metastases. Microtomography revealed bone metastases in ~30% animals of the control group; in experimental groups, no bone metastases were found. The experiment with periosteal (distal epiphysis of the femur) injection of 4T1-Luc2 tumor cells demonstrated pronounced selective effectiveness of Resorba in relation to bone metastases. Monotherapy with Resorba can prevent the development of not only bone, but also visceral metastases of breast cancer.

Modeling and integral X-ray, optical, and MRI visualization of multiorgan metastases of orthotopic 4T1 breast carcinoma in BALB/c mice.

A model of highly metastasizing orthotopic allogeneic breast carcinoma was reproduced and standardized in experiments on BALB/c mice. 4T1 cells characterized by high metastatic activity were transfected with red fluorescent protein (RFP) gene or firefly luciferase (Luc2) gene. Unmodified 4T1 cells and modified 4T1-RFP and 4T1-Luc2 cells were subcutaneously injected to mature female mice into the second mammary fat pads. Quantitative evaluation of the primary node and visceral metastases was performed using magnetic-resonance imaging, X-ray and optical tomography. Modification of 4T1 cells with RFP gene considerably reduced their invasive and metastatic potential and led to spontaneous regression of the primary tumor in 20% cases. Modification of 4T1 cells with Luc2 gene had practically no effect on proliferative, invasive, and metastatic characteristics of the tumor and provided the possibility of quantitative analysis of the primary tumor dynamics by the luminescence intensity. The survival median in mice receiving unmodified 4T1 cells and transfected 4T1-RFP and 4Т1-Luc2 cells was 32, 42, and 38 days, respectively. Neither primary node nor tumor metastases accumulated gadolinium-containing contrast agent and Alasens fluorescent tracer. After implantation of 4T1 and 4Т1-Luc2 cells, multiple metastases were more often detected in the lungs, liver, spleen, spine, and regional lymph nodes and less frequently in the brain, which corresponded to metastasizing profile of human breast cancer. The developed model of orthotopic breast carcinoma 4T1 in BALB/c mice with complex detection of multiple organ metastases using X-ray microCT, optical, and MRI can be recommended for preclinical studies of new antitumor preparations.

[Effect of the constant magnetic field on the chemoluminescence of the skin during its destruction]. / Vliianie postoiannogo magnitnogo polia na khemiliuminestsentsiiu kozhi pri ee destruktsii.

A study was carried out of the effect of constant magnetic field of magnitophore applicator ALM-2 (CMFMA) with magnetic induction B on the surface, in the active centre zone--30 MT and gradient B--5 mT/mm on the intensity of peroxidation of lipids in the human skin during its destruction and under hypothermia. Parameters of ultralow chemoluminescence of skin homogenates initiated by bivalent iron ions were considered as intensity indices of lipid peroxidation. It has been shown that skin incubation for 24 hours under CMFMA effect rules out the strengthening of lipid peroxidation, while it takes place at skin incubation under normal conditions.

[Effect of a constant magnetic field on the respiration of human skin during reparative and destructive processes]. / Vliianie postoiannogo magnitnogo polia na dykhanie kozhi cheloveka pri reparativnykh i destruktivnykh protsessakh.

Effect of magnetophore applicators constant magnetic field (MACMF) on the functional state of human skin at reparative and destructive processes. It has been found in the investigations carried out during epidermatoplasty under the magnetic field effect on the reparation zone for 10--12 days that MACMF effect is of antihypoxic character and is manifested locally and only on a regenerating tissue. In the experiments on skin grafts exposed to magnetic field for 22--26 hours there was also found antihypoxic direction of MACMF effect expressed in the stabilization of tissue respiration, which points to the weakening of destruction.

[Transformation of the strength characteristics and work capacity of antagonistic muscles during rabbit postnatal ontogenesis]. / Osobennosti preobrazovaniia silovykh kharakteristik i rabotosposobnosti myshts-antagonistov v postnatal'nom ontogeneze krolikov

In the rabbit muscles-antagonists in situ, the dependence of work (A) of isotonic contraction of the load (P) was studied in different age periods. For the range of loads 1.5 - Popt greater than or equal to P greater than or equal to 0.5 - Popt, the results were found to be satisfactorily approximated by the equation A = A opt = a - /Popt - P/2, where Aopt, Popt, and a are constants. The experiments revealed that the ratio Aopt. m. gastrocnemius/Aopt. m. tibialis anterior sharply increases during realization of the standing posture (16-18 days) and then drops at the grown-up age. Similar age changes were revealed for the Popt parameters ratio of the same muscles. At the same time, the respective ratio of the a parameters of the muscles under study drops sharply by the 16-18th day age, practically remaining the same afterwards. The obtained changes of the strength parameters and working ability of skeletal muscles in the course of postnatal ontogenesis are regarded from the standpoint of peculiarities of the skeletal muscles functioning at different age periods and with regard to ecological peculiarities of individual development of rabbits.