title: Walker 256 tumor-bearing rats demonstrate altered interstitial cells of Cajal. Effects on ICC in the Walker 256 tumor model.
abstract: BACKGROUND
  Cachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L-glutamine 2% may have beneficial effects in cancer-related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied.
  
  
  METHODS
  Twenty-eight male Wistar rats were divided into four groups: control (C), control supplemented with L-glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L-glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis.
  
  
  RESULTS
  Tumor-bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor-bearing rats compared to controls. L-glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L-glutamine reduced the size of tumors and also tumor-induced cachexia that was not due to altered food intake.
  
  
  CONCLUSIONS
  There are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L-glutamine has differential and complex effects of ICC, it reduces tumor size and tumor-associated cachexia, which supports its beneficial therapeutic role in cancer.
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Fracaro
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: F C V
authors.initials: FC
authors.lastname: Frez
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: B C
authors.initials: BC
authors.lastname: Silva
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: G E
authors.initials: GE
authors.lastname: Vicentini
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: S R G
authors.initials: SR
authors.lastname: de Souza
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: H A
authors.initials: HA
authors.lastname: Martins
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Linden
authors.affiliation: Department of General Pathology, Universidade Estadual de Londrina, Londrina, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Guarnier
authors.affiliation: Department of Morfological Sciences, Universidade Estadual de Maringá, Maringá, Brazil.
authors.forename: J N
authors.initials: JN
authors.lastname: Zanoni
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D015153:Blotting, Western; D002100:Cachexia / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000378:metabolism* / Q000473:pathology; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects*; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D047368:Tumor Burden
chemical_list: C552942:ANO1 protein, rat; D000075369:Anoctamin-1; D018118:Chloride Channels; D005973:Glutamine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat
keywords: antioxidants; cancer; enteric nervous system; immunohistochemistry; intestinal motility