scholarly journals Immunohistochemical Expression of β-catenin, Ki67, CD3 and CD18 in Canine Colorectal Adenomas and Adenocarcinomas

2020 ◽  
Author(s):  
Kristin Marie Valand Herstad ◽  
Gjermund Gunnes ◽  
Runa Rørtveit ◽  
Øyvor Kolbjørnsen ◽  
Linh Tran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumour Progression ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Wilcoxon Test ◽  
Positive Staining ◽  
Expression Levels ◽  
Colonic Cells ◽  
Control Samples

Abstract Background Inflammation is believed to influence the human colorectal carcinogenesis and may have impact upon prognosis and survival. High presence of tumour-infiltrating CD3+ T-cells, is associated with a better outcome in humans with colorectal cancer. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumour-infiltrating immune cells (TIIs) in canine colorectal tumours is associated with histologic indicators of malignancy and can be considered a prognostic factor in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n=18) and adenocarcinoma (n=5) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized of reasons not involving the gastrointestinal tract, served as control tissue (n=9). Results: The tumour samples had significantly lower numbers of CD3+ T- cells in the epithelium compartment (Wilcoxon test, p=0,0006), as well as significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Wilcoxon test, p=0,001). The Ki67 positive cells showed a strong signal in adenomas and adenocarcinomas. There was no clear distinction with regards to expression levels of the markers for tumour progression (β-catenin, and Ki67) between adenomas and adenocarcinomas. Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. When compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (Wilcoxon test, p=0,0002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinoma and adenoma showed moderate to strong staining of the cell nucleus. Conclusions: β-catenin and Ki67 were not useful markers in distinguishing adenomas from adenocarcinomas. The lower presence of CD18- and CD3+ cells in tumours compared to controls, indicates a reduced presence of histiocytes and T-cells which may have implications for the defense against cancer progression.

scholarly journals Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kristin M. V. Herstad ◽  
Gjermund Gunnes ◽  
Runa Rørtveit ◽  
Øyvor Kolbjørnsen ◽  
Linh Tran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Positive Staining ◽  
Colonic Tissue ◽  
Retrospective Case ◽  
Tissue Samples ◽  
Colonic Cells ◽  
Control Samples

Abstract Background Inflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9). Results The tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05). Conclusions β-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.

scholarly journals Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 119
Author(s):  
Tanja Gumpenberger ◽  
Stefanie Brezina ◽  
Pekka Keski-Rahkonen ◽  
Andreas Baierl ◽  
Nivonirina Robinot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Low Risk ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Sporadic Colorectal Cancer ◽  
Molecular Features ◽  
Colorectal Cancer Patients

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the “Metabolomic profiles throughout the continuum of colorectal cancer” (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the “Colorectal Cancer Study of Austria” (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.

scholarly journals Dairy intake during adolescence and risk of colorectal adenoma later in life

2021 ◽  
Author(s):  
Katharina Nimptsch ◽  
Dong Hoon Lee ◽  
Xuehong Zhang ◽  
Mingyang Song ◽  
Maryam S. Farvid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Advanced Adenoma ◽  
Anatomical Site ◽  
Inverse Association ◽  
Dairy Intake ◽  
Dairy Consumption ◽  
Adenoma Risk

Abstract Background Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. Methods In 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. Conclusions In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

scholarly journals Enhancement of Anti-Tumoral Immunity by β-Casomorphin-7 Inhibits Cancer Development and Metastasis of Colorectal Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8232
Author(s):  
Shiori Mori ◽  
Rina Fujiwara-Tani ◽  
Shingo Kishi ◽  
Takamitsu Sasaki ◽  
Hitoshi Ohmori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Cd8 T Cells ◽  
Degradation Product ◽  
Neutral Endopeptidase ◽  
Aberrant Crypt Foci ◽  
Colorectal Carcinogenesis ◽  
Dependent Manner ◽  
Mouse Splenocytes

β-Casomorphin-7 (BCM) is a degradation product of β-casein, a milk component, and has been suggested to affect the immune system. However, its effect on mucosal immunity, especially anti-tumor immunity, in cancer-bearing individuals is not clear. We investigated the effects of BCM on lymphocytes using an in vitro system comprising mouse splenocytes, a mouse colorectal carcinogenesis model, and a mouse orthotopic colorectal cancer model. Treatment of mouse splenocytes with BCM in vitro reduced numbers of cluster of differentiation (CD) 20+ B cells, CD4+ T cells, and regulatory T cells (Tregs), and increased CD8+ T cells. Administration of BCM and the CD10 inhibitor thiorphan (TOP) to mice resulted in similar alterations in the lymphocyte subsets in the spleen and intestinal mucosa. BCM was degraded in a concentration- and time-dependent manner by the neutral endopeptidase CD10, and the formed BCM degradation product did not affect the lymphocyte counts. Furthermore, degradation was completely suppressed by TOP. In the azoxymethane mouse colorectal carcinogenesis model, the incidence of aberrant crypt foci, adenoma, and adenocarcinoma was reduced by co-treatment with BCM and TOP. Furthermore, when CT26 mouse colon cancer cells were inoculated into the cecum of syngeneic BALB/c mice and concurrently treated with BCM and TOP, infiltration of CD8+ T cells was promoted, and tumor growth and liver metastasis were suppressed. These results suggest that by suppressing the BCM degradation system, the anti-tumor effect of BCM is enhanced and it can suppress the development and progression of colorectal cancer.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

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