Limits...
Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans.

Kannen V, de Oliveira EC, Motta BZ, Chaguri AJ, Brunaldi MO, Garcia SB - PLoS Negl Trop Dis (2015)

Bottom Line: An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis.A significant myenteric neuronal denervation was observed.Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.

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.

Conclusion/significance: 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.

Show MeSH

Related in: MedlinePlus

Argyrophilic Nucleolar Organiser Regions (AgNOR) in Chagas megacolon.(A) Illustrative pictures for AgNOR staining in an adenocarcinoma patient. Positive reactions are seen as black dots in the colonocytes nucleus. (A.1) Micrography was taken at 40x magnification (Scale bar = 20 μm). (A.2) Micrography was taken at 100x magnification (Scale bar = 10 μm). (B) Total numbers of AgNOR dots per cell nucleus within the crypt bottom are shown (**P<0.0062 vs CTRL). (C to E) Total numbers of 2 (C; **P<0.005 vs CTRL), 3 (D; *P<0.01 vs CTRL), and 4 (E; ***P<0.0001 vs CTRL) AgNOR dots (+) cells per crypt bottom are shown. Significance was analyzed with the Mann Whitney test. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation. (F) Mean values for percentage difference between megacolon and adenocarcinoma samples are shown according to nuclear distribution of AgNOR dots per nucleus.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4401552&req=5

pntd.0003744.g002: Argyrophilic Nucleolar Organiser Regions (AgNOR) in Chagas megacolon.(A) Illustrative pictures for AgNOR staining in an adenocarcinoma patient. Positive reactions are seen as black dots in the colonocytes nucleus. (A.1) Micrography was taken at 40x magnification (Scale bar = 20 μm). (A.2) Micrography was taken at 100x magnification (Scale bar = 10 μm). (B) Total numbers of AgNOR dots per cell nucleus within the crypt bottom are shown (**P<0.0062 vs CTRL). (C to E) Total numbers of 2 (C; **P<0.005 vs CTRL), 3 (D; *P<0.01 vs CTRL), and 4 (E; ***P<0.0001 vs CTRL) AgNOR dots (+) cells per crypt bottom are shown. Significance was analyzed with the Mann Whitney test. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation. (F) Mean values for percentage difference between megacolon and adenocarcinoma samples are shown according to nuclear distribution of AgNOR dots per nucleus.

Mentions: Analyzing the AgNOR staining within the cryptal bottom revealed however reduced risk for colon cancer in Chagas megacolon patients (Fig 2A and 2B).


Trypanosomiasis-induced megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans.

Kannen V, de Oliveira EC, Motta BZ, Chaguri AJ, Brunaldi MO, Garcia SB - PLoS Negl Trop Dis (2015)

Argyrophilic Nucleolar Organiser Regions (AgNOR) in Chagas megacolon.(A) Illustrative pictures for AgNOR staining in an adenocarcinoma patient. Positive reactions are seen as black dots in the colonocytes nucleus. (A.1) Micrography was taken at 40x magnification (Scale bar = 20 μm). (A.2) Micrography was taken at 100x magnification (Scale bar = 10 μm). (B) Total numbers of AgNOR dots per cell nucleus within the crypt bottom are shown (**P<0.0062 vs CTRL). (C to E) Total numbers of 2 (C; **P<0.005 vs CTRL), 3 (D; *P<0.01 vs CTRL), and 4 (E; ***P<0.0001 vs CTRL) AgNOR dots (+) cells per crypt bottom are shown. Significance was analyzed with the Mann Whitney test. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation. (F) Mean values for percentage difference between megacolon and adenocarcinoma samples are shown according to nuclear distribution of AgNOR dots per nucleus.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401552&req=5

pntd.0003744.g002: Argyrophilic Nucleolar Organiser Regions (AgNOR) in Chagas megacolon.(A) Illustrative pictures for AgNOR staining in an adenocarcinoma patient. Positive reactions are seen as black dots in the colonocytes nucleus. (A.1) Micrography was taken at 40x magnification (Scale bar = 20 μm). (A.2) Micrography was taken at 100x magnification (Scale bar = 10 μm). (B) Total numbers of AgNOR dots per cell nucleus within the crypt bottom are shown (**P<0.0062 vs CTRL). (C to E) Total numbers of 2 (C; **P<0.005 vs CTRL), 3 (D; *P<0.01 vs CTRL), and 4 (E; ***P<0.0001 vs CTRL) AgNOR dots (+) cells per crypt bottom are shown. Significance was analyzed with the Mann Whitney test. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation. (F) Mean values for percentage difference between megacolon and adenocarcinoma samples are shown according to nuclear distribution of AgNOR dots per nucleus.
Mentions: Analyzing the AgNOR staining within the cryptal bottom revealed however reduced risk for colon cancer in Chagas megacolon patients (Fig 2A and 2B).

Bottom Line: An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis.A significant myenteric neuronal denervation was observed.Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil.

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.

Conclusion/significance: 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.

Show MeSH
Related in: MedlinePlus