title: In vitro and in vivo therapeutic approach for a small cell carcinoma of the ovary hypercalcaemic type using a SCCOHT-1 cellular model.
abstract: BACKGROUND
  The small cell ovarian carcinoma of the hypercalcemic type (SCCOHT) which preferably affects young women during regenerative age represents a rare and aggressive form of ovarian tumors with poor prognosis and lacks an efficient therapy.
  
  
  RESULTS
  In vitro chemotherapy testing in a fluorescence assay using a recently developed cellular model from a recurrent SCCOHT revealed sensitivity for certain epothilones, methotrexate and topotecan whereas little if any cytotoxicity was observed with other chemotherapeutics including platin-based compounds. In particular, epothilone B demonstrated a high sensitivity in contrast to ixabepilone with only little detectable effects. Western blot and cell cycle analysis revealed that the epothilone B sensitivity was associated with increased Ser15 phosphorylation of p53, a significant G1 and G2 cell cycle accumulation and subsequent cell death in subG1 phase. Moreover, tubulinβ3 expression in SMARCA4/BRG1-defective SCCOHT-1 in contrast to other ovarian cancer cells was also affected during chemotherapy treatment. Increased extracellular Ca2+ levels further enhanced the epothilone B cytotoxicity in SCCOHT-1 cells. These in vitro effects were also confirmed in vivo in NOD/scid mouse xenografts demonstrating an attenuated tumor growth in epothilone B / Ca2+-treated mice. After 4d of subsequent treatment, the tumor sizes were reduced by about 90% as compared to continuously growing control tumors. In parallel, a hypercalcemia in control tumor-carrying mice was reverted to normal serum Ca2+ levels after epothilone B / Ca2+ therapy.
  
  
  CONCLUSIONS
  Taken together, these data demonstrated anti-tumorigenic effects of epothilone B / Ca2+ in SCCOHT providing a focused therapeutic approach against this rare disease and arising recurrent tumors.
authors.forename: Anna
authors.initials: A
authors.lastname: Otte
authors.forename: Finn
authors.initials: F
authors.lastname: Rauprich
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Juliane
authors.initials: J
authors.lastname: von der Ohe
authors.affiliation: Biochemistry and Tumor Biology Laboratory, Department of Gynecology and Obstetrics Medical, University Hannover, Carl-Neuberg-Str, 1, Hannover, D - 30625, Germany. hass.ralf@mh-hannover.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000150:complications*; D066298:In Vitro Techniques; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000150:complications / Q000628:therapy*
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