title: Orally administered rapamycin, dacarbazine or both for treatment of human melanoma evaluated in severe combined immunodeficiency mice.
abstract: OBJECTIVE
  In this experimental study, the antineoplastic potential of orally administered rapamycin in human melanoma was evaluated and compared with dacarbazine (DTIC) as well as with the antineoplastic effect of the combination of both drugs.
  
  
  METHODS
  The substances were tested using 2 human melanoma cell lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately susceptible. A human melanoma severe combined immunodeficiency mouse xenotransplantation model was used. After development of palpable tumors, mice received oral rapamycin or saline over 18 days. Additionally, from treatment day 4 to 8, mice were randomly chosen to receive either DTIC or saline treatment.
  
  
  RESULTS
  The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in 607B xenografts, no significant tumor weight reduction was observed compared with the saline group (p > 0.05). The combination of rapamycin and DTIC was not superior to rapamycin monotreatment in any cell line.
  
  
  CONCLUSIONS
  These data indicate that oral rapamycin exerts a relevant antineoplastic effect on human melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive melanoma xenografts.
authors.affiliation: Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Thallinger
authors.forename: Sophie
authors.initials: S
authors.lastname: Skorjanec
authors.forename: Afschin
authors.initials: A
authors.lastname: Soleiman
authors.forename: Stanislava
authors.initials: S
authors.lastname: Tzaneva
authors.forename: Johannes
authors.initials: J
authors.lastname: Griss
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rous
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poeppl
authors.forename: Georg
authors.initials: G
authors.lastname: Weinlich
authors.forename: Daniela
authors.initials: D
authors.lastname: Karimian-Teherani
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D020123:Sirolimus / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D003606:Dacarbazine; D020123:Sirolimus