title: Vasostatin increases oxygenation of B16-F10 melanoma tumors and raises therapeutic efficacy of cyclophosphamide.
abstract: One of the preconditions of effective anticancer therapy is efficient transfer of the therapeutic agent (chemotherapeutic) to tumor cells. Fundamental barriers making drug delivery and action difficult include underoxygenation, elevated interstitial pressure, poor and abnormal tumor blood vascular network and acidic tumor milieu. In this study we aimed at developing an optimized scheme of administering a combination of an angiogenesis-inhibiting drug (vasostatin) and a chemotherapeutic (cyclophosphamide) in the therapeutic treatment of mice bearing experimental B16-F10 melanoma tumors. We report that the strongest tumor growth inhibition was observed in mice that received two, three or four vasostatin doses in combination with one injection of cyclophosphamide (i.e., V2 + CTX, V3 + CTX or V4 + CTX schemes). Double administration of vasostatin increases oxygenation of B16-F10 tumors. On the other hand, its five-fold administration lowers tumor oxygenation, breaks down tumor vascular network (increasing hypoxia) and leads in consequence to death of cancer cells and appearance of necrotic areas in the tumor. A decreased cyclophosphamide dose in combination with two doses of vasostatin (V2 + CTX scheme) inhibits tumor growth similarly to a larger dose of cyclophosphamide alone.
authors.affiliation: Center for Translational Research and Molecular Biology of Cancer, Gliwice Branch, Poland. tcichon@io.gliwice.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cichoń
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jarosz
authors.forename: Ryszard
authors.initials: R
authors.lastname: Smolarczyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Ogórek
authors.forename: Sybilla
authors.initials: S
authors.lastname: Matuszczak
authors.forename: Marek
authors.initials: M
authors.lastname: Wagner
authors.forename: Iwona
authors.initials: I
authors.lastname: Mitrus
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sochanik
authors.forename: Joanna
authors.initials: J
authors.lastname: Jazowiecka-Rakus
authors.forename: Stanisław
authors.initials: S
authors.lastname: Szala
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000592:standards / Q000627:therapeutic use*; D037282:Calreticulin / Q000008:administration & dosage / Q000627:therapeutic use*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D024243:HMGB1 Protein; D010446:Peptide Fragments; C121986:vasostatin; D003520:Cyclophosphamide; D010100:Oxygen