title: Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.
abstract: 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.
authors: Research and Educational Center of Medical Nanobiotechnologies, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia. serpoff@mail.ru.|Federal Research Center of Specialized Health Care and Medical Technologies, Federal Medical-Biological Agency, Moscow, Russia. serpoff@mail.ru.
authors: V P
authors: VP
authors: Baklaushev
authors: Department of Fundamental and Applied Neurobiology, V. P. Serbsky Federal Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia.
authors: N F
authors: NF
authors: Grinenko
authors: Department of Fundamental and Applied Neurobiology, V. P. Serbsky Federal Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia.
authors: G M
authors: GM
authors: Yusubalieva
authors: Research and Educational Center of Medical Nanobiotechnologies, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
authors: I L
authors: IL
authors: Gubskii
authors: FARM-Sintez Company, Moscow, Russia.
authors: M S
authors: MS
authors: Burenkov
authors: FARM-Sintez Company, Moscow, Russia.
authors: E Z
authors: EZ
authors: Rabinovich
authors: Research and Educational Center of Medical Nanobiotechnologies, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
authors: N V
authors: NV
authors: Ivanova
authors: Research and Educational Center of Medical Nanobiotechnologies, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.|Department of Fundamental and Applied Neurobiology, V. P. Serbsky Federal Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia.
authors: V P
authors: VP
authors: Chekhonin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D004317:Doxorubicin
keywords: Resorba; bone metastases; culture of 4T1 murine breast carcinoma cells; doxorubicin; zoledronic acid