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

Myenteric neuronal denervation and proliferation in Chagas megacolon.(A) Neurons within the Auersbach’s plexus. Pictures were taken at 100x magnification. Scale bars (10 μm) are inserted. (A.1.) Auersbach’s normal neuronal ganglion is shown within the safety surgical border of an adenocarcinoma patient. Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. (A.2.) Myenteric neuronal degeneration is shown in a Chagas megacolon patient. Blue arrow shows a myenteric degenerated neuron. Black-white arrows indicate gliosis. Black-red arrow leads to a myenteric degenerated glial cell. (B) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (***P<0.0001 vs CTRL). (C) Proliferation was determined given as positive reactions per total crypt cell numbers (iPCNA; ***P<0.0001 vs CTRL). (D) Graph shows the colonocytes numbers per colonic crypt (***P<0.0003 vs CTRL). Significance was analyzed with the Mann Whitney test. Statistical significance was set at p<0.05. Values are shown as the mean ± standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003744.g001: Myenteric neuronal denervation and proliferation in Chagas megacolon.(A) Neurons within the Auersbach’s plexus. Pictures were taken at 100x magnification. Scale bars (10 μm) are inserted. (A.1.) Auersbach’s normal neuronal ganglion is shown within the safety surgical border of an adenocarcinoma patient. Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. (A.2.) Myenteric neuronal degeneration is shown in a Chagas megacolon patient. Blue arrow shows a myenteric degenerated neuron. Black-white arrows indicate gliosis. Black-red arrow leads to a myenteric degenerated glial cell. (B) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (***P<0.0001 vs CTRL). (C) Proliferation was determined given as positive reactions per total crypt cell numbers (iPCNA; ***P<0.0001 vs CTRL). (D) Graph shows the colonocytes numbers per colonic crypt (***P<0.0003 vs CTRL). Significance was analyzed with the Mann Whitney test. Statistical significance was set at p<0.05. Values are shown as the mean ± standard deviation.

Mentions: In spite of potential T. cruzi effects modulating the immune system have been suggested to reduce other tumors besides colon cancer [7–9], how the major T. cruzi effect on the colon, that is the degeneration of myenteric neurons [11], impacts on colon carcinogenesis are not fully understood yet. Indeed, our latest hypothesis suggests the enteric nervous system play a pivotal role in the colon carcinogenesis [19]. Here, histopathological analysis confirmed a significant myenteric neuronal denervation in chagasic megacolon patients (Fig 1A and 1B).


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)

Myenteric neuronal denervation and proliferation in Chagas megacolon.(A) Neurons within the Auersbach’s plexus. Pictures were taken at 100x magnification. Scale bars (10 μm) are inserted. (A.1.) Auersbach’s normal neuronal ganglion is shown within the safety surgical border of an adenocarcinoma patient. Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. (A.2.) Myenteric neuronal degeneration is shown in a Chagas megacolon patient. Blue arrow shows a myenteric degenerated neuron. Black-white arrows indicate gliosis. Black-red arrow leads to a myenteric degenerated glial cell. (B) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (***P<0.0001 vs CTRL). (C) Proliferation was determined given as positive reactions per total crypt cell numbers (iPCNA; ***P<0.0001 vs CTRL). (D) Graph shows the colonocytes numbers per colonic crypt (***P<0.0003 vs CTRL). Significance was analyzed with the Mann Whitney test. Statistical significance was set at p<0.05. Values are shown as the mean ± standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003744.g001: Myenteric neuronal denervation and proliferation in Chagas megacolon.(A) Neurons within the Auersbach’s plexus. Pictures were taken at 100x magnification. Scale bars (10 μm) are inserted. (A.1.) Auersbach’s normal neuronal ganglion is shown within the safety surgical border of an adenocarcinoma patient. Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. (A.2.) Myenteric neuronal degeneration is shown in a Chagas megacolon patient. Blue arrow shows a myenteric degenerated neuron. Black-white arrows indicate gliosis. Black-red arrow leads to a myenteric degenerated glial cell. (B) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (***P<0.0001 vs CTRL). (C) Proliferation was determined given as positive reactions per total crypt cell numbers (iPCNA; ***P<0.0001 vs CTRL). (D) Graph shows the colonocytes numbers per colonic crypt (***P<0.0003 vs CTRL). Significance was analyzed with the Mann Whitney test. Statistical significance was set at p<0.05. Values are shown as the mean ± standard deviation.
Mentions: In spite of potential T. cruzi effects modulating the immune system have been suggested to reduce other tumors besides colon cancer [7–9], how the major T. cruzi effect on the colon, that is the degeneration of myenteric neurons [11], impacts on colon carcinogenesis are not fully understood yet. Indeed, our latest hypothesis suggests the enteric nervous system play a pivotal role in the colon carcinogenesis [19]. Here, histopathological analysis confirmed a significant myenteric neuronal denervation in chagasic megacolon patients (Fig 1A and 1B).

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