title: Effect of the Hedgehog-inhibitor cyclopamine on mice with osteosarcoma             pulmonary metastases.
abstract: Chemoresistant metastases of osteosarcoma in humans limit survival in approximately one third of patients. Furthermore, aggressive chemotherapy can lead to side effects and occurrence of secondary malignancies in long time survivors. Therefore, supplemental medical strategies are worthwhile. The well-directed manipulation of cancer-signaling-cascades is an appealing approach. Targeting of the Hedgehog-pathway in cancer has led to promising results in vitro as well as in vivo in a number of different tumor types. Recently, the impact of cyclopamine, which inhibits Hedgehog signaling by binding to the receptor Smoothened, was shown in different human osteosarcoma cell lines in vitro and in vivo. In the present study we examined the influence of cyclopamine on early pulmonary metastases in vivo. Murine osteosarcoma cells, OS-50, were injected into the lateral tail vein of young BALB/c mice. Treatment with subcutaneous cyclopamine injections began after three days. Two weeks later, the animals were sacrificed and the number of pulmonary metastases was counted. We could observe a trend towards decreased metastases in the cyclopamine group (~20%). On the other hand, remarkable side effects were caused by the cyclopamine/ethanol/triolein preparation (mainly skin ulcerations).
authors.affiliation: Department of Ortho-pedic Surgery, Johann Wolfgang Goethe-University Hospital, Marienburg-strasse 2, D-60528 Frankfurt, Germany. j.warzecha@friedrichsheim.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Warzecha
authors.forename: Daniela
authors.initials: D
authors.lastname: Dinges
authors.forename: Balasz
authors.initials: B
authors.lastname: Kaszap
authors.forename: Dirk
authors.initials: D
authors.lastname: Henrich
authors.forename: Ingo
authors.initials: I
authors.lastname: Marzi
authors.forename: Caroline
authors.initials: C
authors.lastname: Seebach
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine