{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:52:12Z","timestamp":1761519132688,"version":"3.41.0"},"reference-count":58,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:p>Metastatic pheochromocytoma continues to be an incurable disease, and treatment with conventional cytotoxic chemotherapy offers limited efficacy. In the present study, we evaluated a novel topoisomerase I inhibitor, LMP-400, as a potential treatment for this devastating disease. We found a high expression of topoisomerase I in human metastatic pheochromocytoma, providing a basis for the evaluation of a topoisomerase 1 inhibitor as a therapeutic strategy. LMP-400 inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. In a study performed in athymic female mice, LMP-400 demonstrated a significant inhibitory effect on tumor growth with two drug administration regimens. Furthermore, low doses of LMP-400 decreased the protein levels of hypoxia-inducible factor 1 (HIF-1\u03b1), one of a family of factors studied as potential metastatic drivers in these tumors. The HIF-1\u03b1 decrease resulted in changes in the mRNA levels of HIF-1 transcriptional targets. In vitro, LMP-400 showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. We conclude that LMP-400 has promising antitumor activity in preclinical models of metastatic pheochromocytoma and its use should be considered in future clinical trials.<\/jats:p>","DOI":"10.1210\/en.2015-1476","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T17:00:30Z","timestamp":1439398830000},"page":"4094-4104","source":"Crossref","is-referenced-by-count":11,"title":["Inhibitory Effect of the Noncamptothecin Topoisomerase I Inhibitor LMP-400 on Female Mice Models and Human Pheochromocytoma Cells"],"prefix":"10.1210","volume":"156","author":[{"given":"Jan","family":"Schovanek","sequence":"first","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology (J.S., P.B., Y.T., A.G., N.L., S.N., K.P.), Bethesda, Maryland 20892-1109"},{"name":"Department of Internal Medicine III-Nephrology, Rheumatology, and Endocrinology (J.S., Z.F.), Faculty of Medicine and Dentistry, Palacky University, 771 47 Olomouc, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Bullova","sequence":"first","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology (J.S., P.B., Y.T., A.G., N.L., S.N., K.P.), Bethesda, Maryland 20892-1109"},{"name":"Department of Molecular Medicine (P.B., J.K.), Institute of Virology, Slovak Academy of Sciences, 845 05 Bratislava, Slovak Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasin","family":"Tayem","sequence":"first","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology (J.S., P.B., Y.T., A.G., N.L., S.N., K.P.), Bethesda, Maryland 20892-1109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Giubellino","sequence":"first","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology (J.S., P.B., Y.T., A.G., N.L., S.N., K.P.), Bethesda, Maryland 20892-1109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Wesley","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, Warren G. 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