title: Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans.
abstract: BACKGROUND
  Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats.
  
  
  METHODS
  Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards.
  
  
  RESULTS
  No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas' megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced.
  
  
  CONCLUSIONS
  Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research.
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Kannen
authors.affiliation: Department of Surgery, Medical School, Federal University of Goias, Goiania, Brazil.
authors.forename: Enio C
authors.initials: EC
authors.lastname: de Oliveira
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Bruno Zene
authors.initials: BZ
authors.lastname: Motta
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Annuar Jose
authors.initials: AJ
authors.lastname: Chaguri
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Mariângela Ottoboni
authors.initials: MO
authors.lastname: Brunaldi
authors.affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Sérgio B
authors.initials: SB
authors.lastname: Garcia
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D014355:Chagas Disease / Q000150:complications* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology*; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D008531:Megacolon / Q000150:complications* / Q000209:etiology*; D009197:Myenteric Plexus / Q000166:cytology* / Q000469:parasitology; D009474:Neurons / Q000469:parasitology / Q000473:pathology*; D051381:Rats; D018570:Risk Assessment / Q000379:methods; D014349:Trypanosoma cruzi
chemical_list: D014408:Biomarkers, Tumor