title: Z-100, an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B, prevents spontaneous lymphatic metastasis of B16-BL6 melanoma.
abstract: Lymphatic metastasis is common in advanced-stage carcinoma and is associated with a poor prognosis. However, few effective treatments to inhibit it are available. Z-100 is an immunomodulatory extract of Mycobacterium tuberculosis strain Aoyama B that contains polysaccharides such as arabinomannan and mannan. Here, we investigated the inhibitory effect of Z-100 on spontaneous lymphatic metastasis. C57BL/6N mice injected subcutaneously with B16-BL6 melanoma cells in the right hind footpad were administered Z-100 subcutaneously in the right inguinal region on a daily basis. On day twenty-one after the injection, the right inguinal lymph nodes were excised, and the extent of metastasis, the number of immune cells, and the amount of granzyme B protein in the lymph nodes were examined. We also investigated the combined effect of Z-100 and irradiation in this model. Results showed that Z-100 reduced number of animals with metastasis, with respective metastasis rates of 85.7%, 42.9%, 7.1% and 0.0% in saline, 0.1 mg/kg Z-100, 1 mg/kg Z-100 and 10 mg/kg Z-100 group. Further, mice that had been given Z-100 were found to have more immune cells and granzyme B protein in the lymph nodes than control mice. The combination of low dose Z-100 and irradiation also inhibited spontaneous lymph node metastases. These findings suggest that Z-100 may be beneficial in preventing lymphatic metastasis by enhancing the immune response.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Horii
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Seto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Orikawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okamoto
authors.forename: Runa
authors.initials: R
authors.lastname: Eta
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohira
authors.forename: Kokichi
authors.initials: K
authors.lastname: Katsunuma
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hori
authors.forename: Takao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Mineo
authors.initials: M
authors.lastname: Takei
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D053804:Granzymes / Q000378:metabolism; D008055:Lipids / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015182:Lymphatic Irradiation; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008351:Mannans / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009169:Mycobacterium tuberculosis; D016176:T-Lymphocyte Subsets / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama; D053804:Granzymes; C509214:Gzmb protein, mouse