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Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions.

Estofolete CF, Botelho-Machado C, Taboga SR, Zucoloto S, Polli-Lopes AC, Gil CD - Cancer Cell Int. (2010)

Bottom Line: An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers.The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy, School of Medicine - FAMERP, Avenida Brigadeiro Faria Lima 5416, CEP 15090-000, São José do Rio Preto, SP, Brazil. cristiane@famerp.br.

ABSTRACT

Background: In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).

Results: BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.

Conclusions: The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.

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Histological analysis of adenocarcinoma induced by MNNG treatment. A and B) Morphological view of adenocarcinoma (AD) in non-denervated (group III) and denervated stomach (group IV). Muscular layer (M). Intense inflammatory infiltrate (In). C and D) Detail of inflammatory infiltrate of tumor stroma constituted by mast cells (black arrows), neutrophils (arrowheads), lymphocytes (green arrows) and plasma cells (red arrows). Toluidine Blue. Bars: 100 μm (Fig. A and B), 10 μm (Fig. C and D).
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Figure 2: Histological analysis of adenocarcinoma induced by MNNG treatment. A and B) Morphological view of adenocarcinoma (AD) in non-denervated (group III) and denervated stomach (group IV). Muscular layer (M). Intense inflammatory infiltrate (In). C and D) Detail of inflammatory infiltrate of tumor stroma constituted by mast cells (black arrows), neutrophils (arrowheads), lymphocytes (green arrows) and plasma cells (red arrows). Toluidine Blue. Bars: 100 μm (Fig. A and B), 10 μm (Fig. C and D).

Mentions: Non-denervated and denervated stomachs treated with MNNG (groups III and IV, respectively) presented changes in tissue architecture and arrangement of the fibers of the extracellular matrix and an increase of the diameter of pyloric glands as well as in relative volume of the stroma (Fig. 1C, D, G and 1H). Treatment with MNNG induced the development of benign and malign tumors, especially adenomatous polyps and adenocarcinomas (Fig. 1C and 1G) in non-denervated stomachs (group III). Animals with denervated stomachs and treated with MNNG (group IV) developed precancerous lesions and malign tumors characterized by dysplasia, atrophic gastritis and adenocarcinoma (Fig. 1D and 1H). In both groups, the stroma of the adenocarcinomas was enriched by the presence of inflammatory cells, as mast cells, neutrophils, plasma cells and lymphocytes, showing immunological response to neoplasias (Fig. 2). However, the neoplastic lesions of group IV were of smaller and less aggressive profiles when compared to group III, and the inflammatory infiltrate localized in the tumor stroma was more intense, especially in animals that developed adenocarcinomas (Fig. 2D).


Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions.

Estofolete CF, Botelho-Machado C, Taboga SR, Zucoloto S, Polli-Lopes AC, Gil CD - Cancer Cell Int. (2010)

Histological analysis of adenocarcinoma induced by MNNG treatment. A and B) Morphological view of adenocarcinoma (AD) in non-denervated (group III) and denervated stomach (group IV). Muscular layer (M). Intense inflammatory infiltrate (In). C and D) Detail of inflammatory infiltrate of tumor stroma constituted by mast cells (black arrows), neutrophils (arrowheads), lymphocytes (green arrows) and plasma cells (red arrows). Toluidine Blue. Bars: 100 μm (Fig. A and B), 10 μm (Fig. C and D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908609&req=5

Figure 2: Histological analysis of adenocarcinoma induced by MNNG treatment. A and B) Morphological view of adenocarcinoma (AD) in non-denervated (group III) and denervated stomach (group IV). Muscular layer (M). Intense inflammatory infiltrate (In). C and D) Detail of inflammatory infiltrate of tumor stroma constituted by mast cells (black arrows), neutrophils (arrowheads), lymphocytes (green arrows) and plasma cells (red arrows). Toluidine Blue. Bars: 100 μm (Fig. A and B), 10 μm (Fig. C and D).
Mentions: Non-denervated and denervated stomachs treated with MNNG (groups III and IV, respectively) presented changes in tissue architecture and arrangement of the fibers of the extracellular matrix and an increase of the diameter of pyloric glands as well as in relative volume of the stroma (Fig. 1C, D, G and 1H). Treatment with MNNG induced the development of benign and malign tumors, especially adenomatous polyps and adenocarcinomas (Fig. 1C and 1G) in non-denervated stomachs (group III). Animals with denervated stomachs and treated with MNNG (group IV) developed precancerous lesions and malign tumors characterized by dysplasia, atrophic gastritis and adenocarcinoma (Fig. 1D and 1H). In both groups, the stroma of the adenocarcinomas was enriched by the presence of inflammatory cells, as mast cells, neutrophils, plasma cells and lymphocytes, showing immunological response to neoplasias (Fig. 2). However, the neoplastic lesions of group IV were of smaller and less aggressive profiles when compared to group III, and the inflammatory infiltrate localized in the tumor stroma was more intense, especially in animals that developed adenocarcinomas (Fig. 2D).

Bottom Line: An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers.The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy, School of Medicine - FAMERP, Avenida Brigadeiro Faria Lima 5416, CEP 15090-000, São José do Rio Preto, SP, Brazil. cristiane@famerp.br.

ABSTRACT

Background: In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).

Results: BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.

Conclusions: The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.

No MeSH data available.


Related in: MedlinePlus