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 contr...
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| Veröffentlicht in: | Bulletin of experimental biology and medicine 2016-08, Vol.161 (4), p.580-586 |
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| creator | Baklaushev, V. P. Grinenko, N. F. Yusubalieva, G. M. Gubskii, I. L. Burenkov, M. S. Rabinovich, E. Z. Ivanova, N. V. Chekhonin, V. P. |
| description | 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. |
| doi_str_mv | 10.1007/s10517-016-3464-5 |
| format | Article |
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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.</description><identifier>ISSN: 0007-4888</identifier><identifier>EISSN: 1573-8221</identifier><identifier>DOI: 10.1007/s10517-016-3464-5</identifier><identifier>PMID: 27590765</identifier><identifier>CODEN: BEXBAN</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Anthracyclines ; Biomedical and Life Sciences ; Biomedicine ; Bone disorder agents ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer metastasis ; Cancer treatment ; Carcinoma ; Cell Biology ; Development and progression ; Diphosphonates - therapeutic use ; Disease Models, Animal ; Doxorubicin - therapeutic use ; Female ; Imidazoles - therapeutic use ; Internal Medicine ; Laboratory Medicine ; Magnetic Resonance Imaging ; Mammary Neoplasms, Experimental - drug therapy ; Mammary Neoplasms, Experimental - pathology ; Mice ; Mice, Inbred BALB C ; Pathology ; Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)</subject><ispartof>Bulletin of experimental biology and medicine, 2016-08, Vol.161 (4), p.580-586</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>COPYRIGHT 2016 Springer</rights><rights>Bulletin of Experimental Biology and Medicine is a copyright of Springer, 2016.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-c3b1d99dee1cc44f24d2ef2439a411b8f5b64d9b0a0597fc1eb4e48324cb19ff3</citedby><cites>FETCH-LOGICAL-c573t-c3b1d99dee1cc44f24d2ef2439a411b8f5b64d9b0a0597fc1eb4e48324cb19ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10517-016-3464-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10517-016-3464-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27590765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baklaushev, V. P.</creatorcontrib><creatorcontrib>Grinenko, N. F.</creatorcontrib><creatorcontrib>Yusubalieva, G. M.</creatorcontrib><creatorcontrib>Gubskii, I. L.</creatorcontrib><creatorcontrib>Burenkov, M. S.</creatorcontrib><creatorcontrib>Rabinovich, E. Z.</creatorcontrib><creatorcontrib>Ivanova, N. V.</creatorcontrib><creatorcontrib>Chekhonin, V. P.</creatorcontrib><title>Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin</title><title>Bulletin of experimental biology and medicine</title><addtitle>Bull Exp Biol Med</addtitle><addtitle>Bull Exp Biol Med</addtitle><description>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.</description><subject>Animals</subject><subject>Anthracyclines</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone disorder agents</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer metastasis</subject><subject>Cancer treatment</subject><subject>Carcinoma</subject><subject>Cell Biology</subject><subject>Development and progression</subject><subject>Diphosphonates - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>Imidazoles - therapeutic use</subject><subject>Internal Medicine</subject><subject>Laboratory Medicine</subject><subject>Magnetic Resonance Imaging</subject><subject>Mammary Neoplasms, Experimental - drug therapy</subject><subject>Mammary Neoplasms, Experimental - pathology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Pathology</subject><subject>Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)</subject><issn>0007-4888</issn><issn>1573-8221</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kl9vFCEUxYnR2LX6AXwxJCbGl6nAMDPwuF3_Jm18WV98IQxcdmlmYIWZaP30Mm7V1mggkAu_c3IJB6GnlJxRQrpXmZKGdhWhbVXzllfNPbSiTVdXgjF6H61IgSouhDhBj3K-WkrS0ofohHWNJF3brBBcxhArrIPFmzj2PoDF2z0kfbjG0eFLmHQu03_3YYfPE5QKb3QyPsRRY76l-Kuf9vhzHMCmGLzBa-PtT7_X8VtMc-8L-xg9cHrI8ORmP0Wf3r7Zbt5XFx_ffdisLypTup4qU_fUSmkBqDGcO8Ytg7LWUnNKe-GavuVW9kSTRnbOUOg5cFEzbnoqnatP0cuj7yHFLzPkSY0-GxgGHSDOWVHBOiF4TZuCPv8LvYpzCqW7QrVEyFYK9ofa6QGUDy5OSZvFVK25FI2ouVi8zv5BlWFh9CYGcL6c3xG8uCXYgx6mfY7DPPkY8l2QHkGTYs4JnDokP-p0rShRSwbUMQOqZEAtGVCL5tnNy-Z-BPtb8evTC8COQC5XYQfp1tP_6_oDKhC5NQ</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Baklaushev, V. 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P. ; Grinenko, N. F. ; Yusubalieva, G. M. ; Gubskii, I. L. ; Burenkov, M. S. ; Rabinovich, E. Z. ; Ivanova, N. V. ; Chekhonin, V. 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P.</au><au>Grinenko, N. F.</au><au>Yusubalieva, G. M.</au><au>Gubskii, I. L.</au><au>Burenkov, M. S.</au><au>Rabinovich, E. Z.</au><au>Ivanova, N. V.</au><au>Chekhonin, V. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin</atitle><jtitle>Bulletin of experimental biology and medicine</jtitle><stitle>Bull Exp Biol Med</stitle><addtitle>Bull Exp Biol Med</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>161</volume><issue>4</issue><spage>580</spage><epage>586</epage><pages>580-586</pages><issn>0007-4888</issn><eissn>1573-8221</eissn><coden>BEXBAN</coden><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>27590765</pmid><doi>10.1007/s10517-016-3464-5</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Anthracyclines Biomedical and Life Sciences Biomedicine Bone disorder agents Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer metastasis Cancer treatment Carcinoma Cell Biology Development and progression Diphosphonates - therapeutic use Disease Models, Animal Doxorubicin - therapeutic use Female Imidazoles - therapeutic use Internal Medicine Laboratory Medicine Magnetic Resonance Imaging Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - pathology Mice Mice, Inbred BALB C Pathology Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine) |
| title | Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin |
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