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Methods to reduce polyposis and colorectal cancer

A technology for colorectal cancer and polyposis, applied in the field of reducing or inhibiting polyposis and colorectal cancer, can solve the unclarified interaction between polyposis and related colorectal cancer

Inactive Publication Date: 2015-01-28
NORTH CAROLINA STATE UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the interaction of gut microbiota components on polyposis and associated colorectal cancer has not been elucidated

Method used

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  • Methods to reduce polyposis and colorectal cancer
  • Methods to reduce polyposis and colorectal cancer
  • Methods to reduce polyposis and colorectal cancer

Examples

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example 1

[0095] A mouse model of polyposis coli was used to investigate the role of gut microbiota in controlling gastrointestinal immune balance. To analyze the immunomodulatory properties of NCK2025, 5 × 10 8 5-month-old polyp-laden mice were treated orally with a dose of cfu NCK2025, or fed water for 4 weeks as a control. To specifically address the role of LTA, a third group of mice was treated in a similar manner with the parental Lactobacillus acidophilus NCK56. After 4 weeks of treatment, all mice were euthanized and analyzed. NCK56-treated mice showed little change in polyposis compared to control PBS-treated mice. In contrast, the number of polyps in the small intestine of NCK2025-treated mice was reduced ( figure 1 A) and the number of colonic polyps was significantly reduced ( figure 1 A, B). Mitotic and apoptotic activity was significantly reduced in polyps of NCK2025-treated mice compared to PBS- and NCK56-treated mice ( figure 1 C, D). These observations demonstrat...

example 2

[0097] Immunofluorescent staining of paraffin sections of whole colons was performed to provide evidence of suppressed inflammation in NCK2025-treated mice. Previously, the expansion and activation of mast cells in adenomatous polyps was reported, along with evidence for their tumor-promoting role (Khazaie et al. (2011) Cancer Metastasis Rev 30:45 (Khazaie et al., 2011, "(Cancer and Metastasis Review”, Vol. 30, p. 45)). To assess the influence of the gut microbiota on inflammation, intrapolyposis mast cell density was quantified in mice with polyposis treated with NCK2025, compared with fed parental eosinophilic Lactobacillus NCK56 compared to mice fed with NCK2025. A significant reduction in mast cell counts within polyps was observed in mice fed NCK2025, reaching levels equivalent to mast cells in the colon of polyposis-free mice, but found to be less than PBS-treated There was little change in mice compared to NCK56-treated mice ( figure 2 A, D). Polyps are infiltrated w...

example 3

[0100] Previously, we reported that polyposis-associated inflammation became systemic in a mouse model of hereditary polyposis that developed splenomegaly and elevated levels of serum pro-inflammatory cytokines (Gounaris et al .(2008) PLoS One 3: e2916 (Gounaris et al., 2008, PLoS One, Vol. 3, p. e2916)). Aged polyp-laden mice also developed splenomegaly ( Figure 5 A). Treatment with NCK2025 resulted in a significant reduction in spleen size, while treatment with NCK56 showed a similar trend, however it was not statistically significant ( Figure 5 A). Reduced spleen size was associated with increased relative frequency of CD4 effector T-cells and decreased Tregs in the spleen ( Figure 5 B), macrophages and granulocytes decreased ( Figure 5 C) Associated. Similar but not significant trends were also seen in MLN ( Figure 5 B, C). These changes corresponded to a significant decrease in serum levels of IL-10 and pro-inflammatory cytokines but an increase in IL-22 ( I...

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Abstract

Methods for reducing or inhibiting polyposis or colorectal cancer are provided. The methods comprise administering to a mammal a bacterium modified to decrease the display of lipoteichoic acid on the cell surface. Administration of the recombinant bacterium promotes a desired therapeutic response. The recombinant bacterium may be administered in a single dose or series of doses. Methods find use in treating or preventing a variety of polyp-related disorders, for example, treating or Lynch syndrome, familial adenomatous polyposis, and colorectal cancer.

Description

technical field [0001] The present invention relates to methods and compositions for reducing or inhibiting polyposis and colorectal cancer. Background technique [0002] Identifying bacterial components and end products in the gut that increase the ratio of protective to pathogenic inflammation is important for rebalancing homeostasis in gastrointestinal (GI) chronic inflammatory diseases and malignancies. Symbiotic Lactobacillus species are natural microbiota inhabitants in the human gastrointestinal tract and can stimulate innate cells to produce both inflammatory and regulatory cytokines through the interaction of their surface layer proteins. Lipoteichoic acid is a major cell wall component of Lactobacillus and other lactic acid bacteria and has been reported to stimulate dendritic cells (DCs) through specific pattern recognition receptors, including TLR2, leading to cytokine release. Disruption of LTA synthesis by deletion of the phosphoglycerol transferase gene of L....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/74A61K35/741A61K35/744A61K35/747A61P1/00A61P35/00
CPCA61K35/747A61K2300/00A61K35/741A61K35/744A61P1/00A61P35/00A61P43/00
Inventor M·莫哈马扎德托德·克莱恩哈默
Owner NORTH CAROLINA STATE UNIV
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