title: The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma model.
abstract: We investigated the anti-tumor effect of peritumoral resveratrol in combination with immunotherapy in vivo in neuroblastoma-bearing mice. Subcutaneous NXS2 tumors were induced in A/J mice. On day 10, some mice received 15 mcg of intravenous immunocytokine for 5 days, mice received 20 mg of peritumoral resveratrol twice a week (starting on day 12) for a total of 5 injections, and a separate group received a combination of both regimens. Tumor progression and survival were assessed every 3-4 days. Blood and primary tumor tissue samples were collected on day 20 for Complete Blood Count and CD45 immunohistochemistry and histology, respectively. The primary tumor regressed in all mice receiving peritumoral resveratrol. Most of these mice receiving peritumoral resveratrol alone developed metastatic tumors and recurrence of the primary tumor after cessation of therapy. When resveratrol and immunocytokine regimens were combined, 61% of the mice receiving this combination therapy resolved their primary tumors and survived without developing metastatic tumors, compared to 15 and 13% receiving resveratrol or immunocytokine alone, respectively. None of the therapeutic regimes prevented lymphocyte infiltration or affected the complete blood count. Greater necrosis was observed microscopically in tumors from mice receiving the combination therapy. These results demonstrate that the combination therapy of peritumoral resveratrol plus intravenous immunocytokine provides better anti-tumor effects in this model than either therapy alone.
authors.affiliation: Department of Human Oncology, University of Wisconsin, Madison, WI 53792, USA.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Soto
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Hank
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Van De Voort
authors.forename: Lalita
authors.initials: L
authors.lastname: Subramanian
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Polans
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Rakhmilevich
authors.forename: Richard K
authors.initials: RK
authors.lastname: Yang
authors.forename: Songwong
authors.initials: S
authors.lastname: Seo
authors.forename: KyungMann
authors.initials: K
authors.lastname: Kim
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gillies
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D005732:Gangliosides / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D009364:Neoplasm Recurrence, Local; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy*; D000077185:Resveratrol; D013267:Stilbenes / Q000097:blood / Q000627:therapeutic use*; D013534:Survival; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D005732:Gangliosides; D007074:Immunoglobulin G; D007376:Interleukin-2; D013267:Stilbenes; C019403:ganglioside, GD2; D017493:Leukocyte Common Antigens; D000077185:Resveratrol