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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.

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Related in: MedlinePlus

Myenteric neuronal denervation and colon preneoplastic lesions in rats.(A) Illustrative pictures for normal (A.1) and preneoplastic (A.2; severe dysplasia) colon tissues from a carcinogen-exposed rat. (B) Illustrative pictures for normal (B.1) and degenerated (B.2) myenteric plexus in uninfected (B.1) and infected T. cruzi rats (B.2). Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. Blue arrow shows a myenteric degenerated neuron. Black-red arrow leads to a myenteric degenerated glial cell. (C) Total (T.) numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (DMH, 1,2 dimethylhidrazine; BAC, benzalkonium chloride; **P<0.01 vs DMH). (D) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (*P<0.05 vs DMH). Significance in the C and D graphs was analyzed by the Two-way ANOVA with Bonferroni’s posttest. (E) T. numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (#P<0.05 vs D; **P<0.01 vs DH). (F) M. neuronal density was determined the number of myenteric neurons per T. number of colonic crypts in each sample (##P<0.01 vs D; *P<0.05 vs DH). Significance in the E and F graphs was analyzed by the One-way ANOVA with Dunn’s posttest. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation.
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pntd.0003744.g003: Myenteric neuronal denervation and colon preneoplastic lesions in rats.(A) Illustrative pictures for normal (A.1) and preneoplastic (A.2; severe dysplasia) colon tissues from a carcinogen-exposed rat. (B) Illustrative pictures for normal (B.1) and degenerated (B.2) myenteric plexus in uninfected (B.1) and infected T. cruzi rats (B.2). Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. Blue arrow shows a myenteric degenerated neuron. Black-red arrow leads to a myenteric degenerated glial cell. (C) Total (T.) numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (DMH, 1,2 dimethylhidrazine; BAC, benzalkonium chloride; **P<0.01 vs DMH). (D) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (*P<0.05 vs DMH). Significance in the C and D graphs was analyzed by the Two-way ANOVA with Bonferroni’s posttest. (E) T. numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (#P<0.05 vs D; **P<0.01 vs DH). (F) M. neuronal density was determined the number of myenteric neurons per T. number of colonic crypts in each sample (##P<0.01 vs D; *P<0.05 vs DH). Significance in the E and F graphs was analyzed by the One-way ANOVA with Dunn’s posttest. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation.

Mentions: Ascertaining the relationship between myenteric neuronal activity and colon carcinogenesis, in vivo experiments were performed. Rats were weekly exposed to a carcinogen after 86-days from T. cruzi infection. Following those 12-wks of carcinogenic exposure, T. cruzi-infected rats developed significant less colon preneoplastic lesions than their uninfected control group (Fig 3A; DMH, 2.89 ± 2.1 vs T. cruzi+DMH, 1.05 ± 0.94 T. dysplastic lesions per mm2; p<0.04).


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 colon preneoplastic lesions in rats.(A) Illustrative pictures for normal (A.1) and preneoplastic (A.2; severe dysplasia) colon tissues from a carcinogen-exposed rat. (B) Illustrative pictures for normal (B.1) and degenerated (B.2) myenteric plexus in uninfected (B.1) and infected T. cruzi rats (B.2). Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. Blue arrow shows a myenteric degenerated neuron. Black-red arrow leads to a myenteric degenerated glial cell. (C) Total (T.) numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (DMH, 1,2 dimethylhidrazine; BAC, benzalkonium chloride; **P<0.01 vs DMH). (D) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (*P<0.05 vs DMH). Significance in the C and D graphs was analyzed by the Two-way ANOVA with Bonferroni’s posttest. (E) T. numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (#P<0.05 vs D; **P<0.01 vs DH). (F) M. neuronal density was determined the number of myenteric neurons per T. number of colonic crypts in each sample (##P<0.01 vs D; *P<0.05 vs DH). Significance in the E and F graphs was analyzed by the One-way ANOVA with Dunn’s posttest. 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.g003: Myenteric neuronal denervation and colon preneoplastic lesions in rats.(A) Illustrative pictures for normal (A.1) and preneoplastic (A.2; severe dysplasia) colon tissues from a carcinogen-exposed rat. (B) Illustrative pictures for normal (B.1) and degenerated (B.2) myenteric plexus in uninfected (B.1) and infected T. cruzi rats (B.2). Black arrow shows a myenteric neuron, while red arrow leads to a myenteric glial cell. Blue arrow shows a myenteric degenerated neuron. Black-red arrow leads to a myenteric degenerated glial cell. (C) Total (T.) numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (DMH, 1,2 dimethylhidrazine; BAC, benzalkonium chloride; **P<0.01 vs DMH). (D) Myenteric (M.) neuronal density was determined the number of myenteric neurons per total (T.) number of colonic crypts in each sample (*P<0.05 vs DMH). Significance in the C and D graphs was analyzed by the Two-way ANOVA with Bonferroni’s posttest. (E) T. numbers of colon dysplastic lesions per mm2 are shown in carcinogen-exposed groups (#P<0.05 vs D; **P<0.01 vs DH). (F) M. neuronal density was determined the number of myenteric neurons per T. number of colonic crypts in each sample (##P<0.01 vs D; *P<0.05 vs DH). Significance in the E and F graphs was analyzed by the One-way ANOVA with Dunn’s posttest. Statistical significance was set at P<0.05. Values are shown as the mean ± standard deviation.
Mentions: Ascertaining the relationship between myenteric neuronal activity and colon carcinogenesis, in vivo experiments were performed. Rats were weekly exposed to a carcinogen after 86-days from T. cruzi infection. Following those 12-wks of carcinogenic exposure, T. cruzi-infected rats developed significant less colon preneoplastic lesions than their uninfected control group (Fig 3A; DMH, 2.89 ± 2.1 vs T. cruzi+DMH, 1.05 ± 0.94 T. dysplastic lesions per mm2; p<0.04).

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