Toll-like receptors and the tendency of normal mucous membrane to transform to polyp or colorectal cancer

The aim of the study was to study and evaluate the predictive value of the immune microenvironment of gastric cancer and morphologically normal mucous membrane of the peritumoral area using an automatic morphometric analysis system on the example of CD 8+ cells.Material and Methods. Surgical samples from 130 patients with a verified diagnosis of gastric cancer were used. After immunohistochemical staining with antibodies to CD 8, a morphological assessment was performed according to the original method. We assessed the average area of CD 8+ cells in three fields of view (lens magn. ×20) using the automatic system of morphometric analysis LAS X (Leica) in the central part of the tumor and areas of morphologically normal mucous membrane of the peritumoral region directly adjacent to the tumor tissue. The results were compared with the main clinical and morphological characteristics of the tumor as well as with the overall five-year survival of patients.Results and Discussion. A high density of CD 8+ infiltration of normal mucous membrane of the peritumoral area was observed in groups T4a and T4b by the depth of invasion (n=96, p=0.0089) and was associated with the presence of emboli in the lymphatic vessels (n=96, p=0.0102) and with the more advanced stage of gastric cancer (n=96, p=0.0107). The studied cases were divided into two groups: less than 3300 square micrometers (better patient survival; n=79, p=0.01) and more than 3300 square micrometers according to the average area of CD 8+ cells in normal mucous membrane of the peritumoral area. According to multivariate survival analysis using the Cox regression model, it was found that the average area of CD 8+ cells in normal mucous membrane of the peritumoral area was a significant negative prognostic factor (RR=1.537; CI : 0.761–3.105; p<0.01) comparable in degree covariance with the stage of the tumor A similar indicator assessed in central part of the tumor was not significantly associated with patient survival (RR=0.803; CI : 0.574–1.122; p>0.05).Conclusion. The possibility of using an automatic analysis system to evaluate the immune microenvironment in gastric cancer was demonstrated for the first time. It was found that a high level of CD 8+ lymphocyte infiltration of morphologically normal mucous membrane of the peritumoral area was an independent negative prognostic factor. Therefore, we recommend the mandatory preoperative biopsy sampling from the mucous membrane of the peritumoral region for morphometric assessment of CD 8+ lymphocyte infiltration.

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Effect of Cold Exposure and Capsaicin on the Expression of Histone Acetylation and Toll-like Receptors in 1,2-dimethylhydrazine-induced Colon Carcinogenesis

10.21203/rs.3.rs-332786/v1 ◽

2021 ◽

Author(s):

Jingchun Qin ◽

Huixuan Li ◽

Weitao Yu ◽

Li Wei ◽

Bin Wen

Keyword(s):

Colorectal Cancer ◽

Western Blot ◽

Histone Acetylation ◽

Cold Exposure ◽

Quantitative Polymerase Chain Reaction ◽

Histone H3 ◽

Tumor Incidence ◽

Mrna Levels ◽

Colon Mucosa ◽

Toll Like Receptors

Abstract Previous studies have indicated that capsaicin-rich diet and cold weather have showed strong association with tumor incidence. Thus, we investigated the effects of capsaicin and cold exposure in 1,2-dimethylhydrazine-induced colorectal cancer as well as the mechanisms underlying capsaicin and cold induced CRC. Rats were randomly divided into four groups and received cold still water and capsaicin via intragastric gavage until the end of the experiment. The rat’s body weight, thymus weight, and food intakes were assessed. Global levels of histone H3K9, H3K18, H3K27, H4K16 acetylation and, histone deacetylase (HDACs) in colon mucosa were assessed by western blot. Expression levels of Toll-like receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) were measured by western-blot and reverse-transcriptase quantitative polymerase chain reaction (qPCR). We found that cold and low-does capsaicin increased tumor numbers and multiplicity, although there were no differences in tumor incidence. Additionally, rat exposure of cold water and capsaicin display further higher levels of histone H3 lysine 9 (H3K9AC), histone H3 lysine 18 (H3K18AC), histone H3 lysine 27 (H3K27AC) and HDACs compared with the DMH and normal rats. In contrast, a considerable decrease of histone H4 lysine 16 (H4K16AC) was detected in the colon mucosa. Cold and low-dose capsaicin exposure group were also increased TLR2 and TLR4 proteins levels and mRNA levels. These results suggest that chronic cold exposure and capsaicin at a low-does intervention exacerbate ectopic expression of global histone acetylation and TLR level, which are crucial mechanisms responsible for the progression of colorectal cancer in rat.

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Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in colorectal cancer

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i26.4831 ◽

2017 ◽

Vol 23 (26) ◽

pp. 4831 ◽

Cited By ~ 11

Author(s):

Karoliina Paarnio ◽

Sara Väyrynen ◽

Kai Klintrup ◽

Pasi Ohtonen ◽

Markus J Mäkinen ◽

...

Keyword(s):

Colorectal Cancer ◽

Toll Like Receptors

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The Association between Gut Microbiota and Intestinal Toll-like Receptors Genes Expression in Adenomatous and Colorectal Cancerous patients

10.21203/rs.2.23741/v1 ◽

2020 ◽

Author(s):

Sama Rezasoltani ◽

Maryam Sharafkhah ◽

Hamid Asadzadeh Aghdaei ◽

Meysam Olfatifar ◽

Ehsan Nazemalhosseini Mojarad ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Bacteroides Fragilis ◽

Normal Group ◽

Adenomatous Polyposis ◽

Toll Like Receptors ◽

Genes Expression

Abstract Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, AP and CRC groups. The genes expression of TLR2, TLR4 and TLR5 were significantly different in AP and CRC cases vs. normal group (P value <0.05). There was a significant relationship between TLR2, TLR4, TLR5 genes expression and Roseburia spp., P. gingivalis and ETBF quantity in normal group. Also significant association between TLR2, TLR4 genes expression levels and the quantity of S.bovis , ETBF, Roseburia spp. and E. faecalis in AP and CRC cases were achieved. Conclusion : Intestinal expression of TLR2, TLR4 and TLR5 is dynamic and depends on gut microbiota. Hence, altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a group of patients with AP and CRC. Keyword: Adenomatous polyposis; colorectal cancer; gut microbiota; Toll-like receptors; intestinal inflammation

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Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

Oman Medical Journal ◽

10.5001/omj.2015.89 ◽

2015 ◽

Vol 30 (6) ◽

pp. 455-460 ◽

Cited By ~ 3

Author(s):

Nasrollah Saghravanian ◽

Narges Ghazi ◽

Zahra Meshkat ◽

Nooshin Mohtasham

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Mucous Membrane ◽

Squamous Cell ◽

Verrucous Carcinoma ◽

Oral Leukoplakia ◽

Carcinoma Squamous Cell ◽

Normal Mucous Membrane

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Toll-like receptors in the inflammatory response during open and laparoscopic colectomy for colorectal cancer

Surgical Endoscopy ◽

10.1007/s00464-011-1871-2 ◽

2011 ◽

Vol 26 (2) ◽

pp. 330-336 ◽

Cited By ~ 22

Author(s):

Konstantinos E. Tsimogiannis ◽

Constantinos C. Tellis ◽

Alexandros D. Tselepis ◽

George K. Pappas-Gogos ◽

Evangelos C. Tsimoyiannis ◽

...

Keyword(s):

Colorectal Cancer ◽

Inflammatory Response ◽

Laparoscopic Colectomy ◽

Toll Like Receptors

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MODERN ENDOSCOPIC CLASSIFICATIONS OF EPITHELIAL NOEPLASMS IN COLON. THEIR ROLE IN MANAGEMENT OF PATIENTS

Health and Ecology Issues ◽

10.51523/2708-6011.2016-13-3-4 ◽

2016 ◽

pp. 19-24

Author(s):

N. A. Lagodich ◽

A. V. Varabei ◽

A. M. Mahmudov

Keyword(s):

Colorectal Cancer ◽

High Resolution ◽

Real Time ◽

Mucous Membrane ◽

Malignant Tumors ◽

Preventive Measure ◽

Early Diagnostics ◽

Endoscopic Equipment ◽

Mucosal Resection ◽

Submucosal Dissection

Early diagnostics and removal of precancer lesions of the mucous membrane in the colon are recognized as a modern preventive measure against colorectal cancer. Thanks to the development of endoscopic equipment and emergence of systems of high resolution, the idea about the morphology of predecessors of malignant tumors has changed. It has become possible to predict the histologic structure of the epithelial mass in real time. Notions about situations when one should resort to standard polypectomia, mucosal resection or submucosal dissection have been so far formed.

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