title: Inhalation therapy with M1 inhibits experimental melanoma development and metastases in mice.
abstract: BACKGROUND
  M1 is a homeopathic medicine with immunostimulatory properties used mainly by cancer patients to complement current therapies. Metastatic melanoma is a skin-originated form of cancer without a single therapy able to produce high rate and sustained responses, which attracts the use of complementary therapies such as M1. However, M1's anti-melanoma effects remain to be pre-clinically demonstrated. Therefore in the present work, we utilized a pulmonary metastatic melanoma model and a subcutaneous melanoma growth model to investigate the potential benefits of treatment with M1.
  
  
  METHODS
  C57BL/6 mice were injected intravenously or subcutaneously with B16F10 mouse melanoma cells. After 24 h, mice were treated with either M1 or vehicle (water) for 14 days, euthanized and harvested for multi-parameter pulmonary and tumor analyses.
  
  
  RESULTS
  Mice treated with M1 had significantly lower tumor burden in the lungs and subcutaneous tissue than control mice. Furthermore, tumors were impaired in proliferation and tumor related angiogenesis by the inhibition of myeloid derived suppressor cells (MDSC) positive for angiotensin II type 1 receptor (AT1R).
  
  
  CONCLUSIONS
  Altogether these data suggest M1 is an efficient candidate for melanoma therapy to be considered for future clinic studies as this study is the first supporting the idea that melanoma patients may benefit with the treatment. The treatment with M1 provides advantages considering the highly-diluted properties and a cost effective alternative to costly chemotherapeutic approaches with, if any, lower toxicity.
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Ferrari de Andrade
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Département d'Immunologie, 25-28 rue du Docteur Roux, 75724, Paris, France. Electronic address: brian.mozeleski@gmail.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Mozeleski
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Aline Raquell
authors.initials: AR
authors.lastname: Leck
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Cleber Rafael Vieira
authors.initials: CR
authors.lastname: da Costa
authors.affiliation: Queensland Institute of Medical Research, Immunology in Cancer and Infection, 300 Herston Rd, Brisbane, QLD, 4006, Australia. Electronic address: fernando.guimaraes@qimrberghofer.edu.au.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Souza Fonseca Guimarães
authors.affiliation: Pontifícia Universidade Católica do Paraná, Biotério Central, 155, Imaculada Conceição, Bairro Prado Velho, Curitiba, PR, 80215-901, Brazil. Electronic address: rafael.zotz@pucpr.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Zotz
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Katia
authors.initials: K
authors.lastname: Fialho do Nascimento
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Camargo de Oliveira
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil.
authors.forename: Dorly
authors.initials: D
authors.lastname: de Freitas Buchi
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Biologia Celular, Laboratório de Células Inflamatórias e Neoplásicas, Coronel Francisco Heráclito dos Santos, Curitiba, PR, 81530-900, Brazil. Electronic address: labbiocel@ufpr.br.
authors.forename: Edvaldo
authors.initials: E
authors.lastname: da Silva Trindade
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006705:Homeopathy / Q000379:methods*; D008419:Materia Medica / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D012138:Respiratory Therapy / Q000379:methods*
chemical_list: D008419:Materia Medica
keywords: Angiogenesis; Angiotensin II receptor; Homeopathy; M1; Melanoma; Tumor growth