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

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.

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

10.21203/rs.3.rs-48802/v1 ◽

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.

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STUDY OF TUMOR MICROENVIRONMENT AND HOST RESPONSE IN COLORECTAL CANCER: IMMUNOHISTOCHEMICAL AND CLINICOPATHOLOGICAL APPROACH

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i1.35940 ◽

2019 ◽

pp. 32-37

Author(s):

NORIA OTHMAN RAFFALLA ◽

SUZAN MOHAMED FAROUK HELAL ◽

AMANY ABD EL-BARY ABD EL-LATIF ◽

RASHA OMAR ELSAKA

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

T Cells ◽

Tumor Microenvironment ◽

Regulatory T Cells ◽

Cytotoxic T Cells ◽

Tumor Infiltrating Lymphocytes ◽

Tumor Associated Macrophages ◽

Tissue Samples ◽

Level Of Significance

Objective: This study aimed to evaluate the immunohistochemical expression of forkhead boxP3 (Foxp3), CD8, CD68, and CD21 in stroma between tumor cells of colorectal cancer (CRC) patients and examines the relationship between these variables and clinicopathological parameter and patients’ prognosis. Methods: In this work, 50 cases of colorectal carcinomas were included and immunohistochemical evaluation of Foxp3, CD8, CD68, and CD21 in tumor tissue samples. Results: Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells and regulatory T cells as well as tumor-associated macrophages and follicular dendritic cells (FDCs) were studied in the stroma of the tumor using immunostaining technique for CD8, Foxp3, CD68, and CD21, respectively. Cases were followed up. CD8-positive cytotoxic T cells, Foxp3-positive regulatory T cells, and CD21 positive-FDCs were significantly more pronounced in early tumors and those with longer overall survival. On the other hand, CD68 positive macrophages were more encountered in late stage and metastatic tumors as well as tumors with shorter overall survival, but these results not reached the level of significance. Conclusion: We concluded that (TILs) and FDCs are conferring better prognosis in CRCs, they may act synergistically in stimulating a protective immune response in the tumor microenvironment that hinders tumor progression, while the role of tumor-associated macrophages in CRCs is still controversial and needs further studies.

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Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.6244 ◽

2010 ◽

Vol 28 (30) ◽

pp. 4575-4580 ◽

Cited By ~ 62

Author(s):

Rachel S. Midgley ◽

Christopher C. McConkey ◽

Elaine C. Johnstone ◽

Janet A. Dunn ◽

Justine L. Smith ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinogenesis ◽

Phase Iii ◽

Adjuvant Setting ◽

Case Control Studies ◽

Curative Surgery ◽

Tissue Samples ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Cox 2

Purpose Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC). Patients and Methods Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome. Results Two thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed. Conclusion In this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors.

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

Metabolites ◽

10.3390/metabo11020119 ◽

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.

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Detection of DNA stool mutations in colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22074 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22074-e22074

Author(s):

Nora Manoukian Forones ◽

Jacqueline Miranda Lima ◽

Yolanda Teixeira ◽

Celia Aparecida Marques Pimenta ◽

Helena Murray ◽

...

Keyword(s):

Colorectal Cancer ◽

Sanger Sequencing ◽

Tissue Sample ◽

Simultaneous Detection ◽

High Specificity ◽

Screening Tests ◽

Common Mutation ◽

Tissue Samples ◽

Human Dna ◽

Control Samples

e22074 Background: Colorectal cancer (CRC) is the third leading cause of cancer in the world. Noninvasive screening tests have higher compliance. Changes in tumoral cells are also found in the stools after cancer cell exfoliation. Aim: to detect mutations in the stools of CRC patients and compare to mutations found in CRC tissue Methods: Patients referred for colonoscopy were divided into 3 groups: control, cancer, and polyp. The DNA was extracted from tissue and stool and it was analysed by two microarrays, the KRAS/BRAF/PIK3CA Array and the RanplexCRC Array (Randox Laboratories Ltd). Both based on the simultaneous detection of 20 mutations in KRAS, BRAF and PIK3CA and 28 mutations in KRAS, BRAF, TP53 and APC respectively. Positive tissue sample mutations were confirmed by Sanger sequencing. Results: 90 stools and 112 tissue biopsies were studied. Analysis of tissue samples was initially performed using the KRAS/BRAF/PIK3CA Array. In total mutations were detected in 16(55%) CRC, 12(45%) polyp and 2(6%) control samples. Mutations were confirmed via Sanger sequencing (76%). In the stool the frequency were 17(35%) in CRC, 10(71%) in polyp and 1(4%) in the control. Inconclusive tests were higher among the controls (32.5%) and polyps (22%), being less frequent in the CRC patients (6%). Excluding the inconclusive tests, WT genes were common in the controls (96%). The most common mutation was within KRAS codon 12. Stools samples from 48 subjects were compared to the results obtained by the RanplexCRC Array and mutations were found in 50% of CRC. KRAS/BRAF/PIK3CA Array stool results had a correlation with RanplexCRC Array in 64% of CRC patients and in 47% of polyp patients. The average human DNA in the stools was 15ng/ul in CRC patients and 0.46ng/ul in the controls (p=0.0001). Conclusions: Both arrays had a good correlation and a sensitivity between 30-50% with a high specificity (95-100%). The KRAS/BRAF/PIK3CA Array is currently optimized and recommended for assessment of tissue samples. This initial set of data however does indicate its potential applicability to stool specimens. Inconclusive tests are likely as a result of limited human DNA content within stool control samples. FAPESP (Sao Paulo Research Foundation) project 09/16618-8.

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Initial correlative studies from a trial of cetuximab and pembrolizumab in metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4062 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4062-4062

Author(s):

Patrick M Boland ◽

Jason Muhitch ◽

Scott I Abrams ◽

Orla Maguire ◽

Hans Minderman ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Metastatic Colorectal Cancer ◽

Clinical Data ◽

Cytotoxic T Cell ◽

Tissue Samples ◽

Tumor Tissues ◽

Tumor Biopsies ◽

The Impact ◽

Clinical Trial Information

4062 Background: Cetuximab is an EGFR-targeting IgG1 mAb. Pre-clinical data suggests cetuximab induces CD8+ cytotoxic T-cell (CTL) infiltration of tumors. We hypothesized that augmentation of CTLs in the tumor microenvironment (TME) may provide the proper milieu for effective PD-1 inhibition in metastatic colorectal cancer (mCRC). We conducted a phase Ib/II study of cetuximab with the PD-1 antibody, pembrolizumab, in mCRC. Correlative blood and tissue samples were collected to assess the impact of this treatment on CTLs, as well as potential compensatory alterations in regulatory T-cells (Tregs) and suppressive MDSCs (NCT02713373). Methods: 3 week treatment cycles included pembrolizumab at 200 mg on day 1 and cetuximab 250 mg/m2 following the 400 mg/m2 loading dose. Tumor biopsies were obtained at baseline and at c4d1 (Day 64). Peripheral blood (PB) was drawn at baseline, c2d1 (day 22) and c4d1 (Day 64). Flow cytometry was performed within 24 hours with additional samples stored for future analysis. In the present analysis, we assessed changes in levels of the cellular populations of interest between cycle 4 and cycle 1. Results: Forty-two RAS-wt patients were enrolled through October 2019. Paired tumor tissues were successfully analyzed for 16 patients and PB for 38. Intratumoral CTLs (CD3+CD8+) increased significantly (+47%, p < .05). In PB, there was a slight overall decrease in PB CTLs (-5%, p = NS) and a significant decrease in CD8+CD45RO+PD1+ cells (-42%, p < .05). We saw simultaneous decreases in PD-1+ CTLs in the tumor and PB. There was a trend for increase in Tregs (CD4+ Cd25+ FoxP3+) in PB (+11%, p = NS), but an overall increase in the Teff:Treg ratio (+30%, p = NS). CD4+CTLA4+ cells significantly increased (+37%, p < .05). Granulocytic MDSCs (CD11b+CD14−CD33+HLADR−) in PB decreased significantly on-treatment (-30%, p < 0.5). The sample size and tissue limitations prohibited meaningful evaluation of tissue Tregs and MDSCs via the present methods. Conclusions: Cetuximab and pembrolizumab induced dynamic changes in the TME and PB. The treatment associated increase in intratumoral CTLs was particularly pronounced, consistent with their local expansion and/or influx. This was accompanied by a decrease in PB CTLs. Decreases in multiple PD-1+ lymphoid populations were observed in both tumor and PB, notably PD-1+ CTLs. Of note, we saw a synchronous increase in immunosuppressive CD4+CTLA4+ T-cells in PB. Patient outcomes are pending maturation. Further analyses are planned, coupled with integration of clinical data. Clinical trial information: NCT02713373 .

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Liposomal Irinotecan for Treatment of Colorectal Cancer in a Preclinical Model

Cancers ◽

10.3390/cancers11030281 ◽

2019 ◽

Vol 11 (3) ◽

pp. 281 ◽

Cited By ~ 2

Author(s):

Jiao-Ren Huang ◽

Mei-Hsien Lee ◽

Wen-Shan Li ◽

Han-Chun Wu

Keyword(s):

Colorectal Cancer ◽

Active Form ◽

Treated Group ◽

Preclinical Model ◽

Colonic Tissue ◽

First Line ◽

Tissue Samples ◽

Clinical Benefits ◽

Hematoxylin And Eosin ◽

Liposomal Irinotecan

Colorectal cancer (CRC) is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Because of the use of first-line CRC treatments, such as irinotecan (IRI), is hindered by dose-limiting side effects, improved drug delivery systems may have major clinical benefits for CRC treatment. In this study, we generate and characterize liposomal irinotecan (Lipo-IRI), a lipid-based nanoparticle, which shows excellent bioavailability and pharmacokinetics. Additionally, this formulation allows IRI to be maintained in active form and prolongs its half-life in circulation compared to IRI in solution. Compared with IRI statistically, the level of prostaglandin E2 (PGE2) in colonic tissue decreases, and Bifidobacterium spp. (beneficial intestinal microbiota) content increases in the Lipo-IRI-treated group. Moreover, no damage is observed by the hematoxylin and eosin staining of the normal tissue samples from the Lipo-IRI-treated group. In a xenograft mouse model, CRC tumors shrink markedly following Lipo-IRI treatment, and mice receiving a targeted combination of Lipo-IRI and liposomal doxorubicin (Lipo-Dox) extend their survival rate significantly. Overall, our results demonstrate that this formulation of Lipo-IRI shows a great potential for the treatment of colorectal cancer.

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The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival

Analytical Cellular Pathology ◽

10.1155/2010/673592 ◽

2010 ◽

Vol 33 (5-6) ◽

pp. 177-189 ◽

Cited By ~ 15

Author(s):

Anna G. Antonacopoulou ◽

Konstantina Floratou ◽

Vasiliki Bravou ◽

Anastasia Kottorou ◽

Fotinos-Ioannis Dimitrakopoulos ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Splice Variant ◽

Splice Variants ◽

Colorectal Carcinogenesis ◽

Clinicopathological Parameters ◽

Mrna Levels ◽

Colorectal Carcinomas ◽

Tissue Samples ◽

Survivin Protein

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.

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Detection of Fusobaterium nucleatum in feces and colorectal mucosa as a risk factor for colorectal cancer: a systematic review and meta-analysis

Systematic Reviews ◽

10.1186/s13643-020-01526-z ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Amal Idrissi Janati ◽

Igor Karp ◽

Claudie Laprise ◽

Hisham Sabri ◽

Elham Emami

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Systematic Reviews ◽

Meta Analysis ◽

Positive Association ◽

Fusobacterium Nucleatum ◽

Relevant Information ◽

Colorectal Carcinogenesis ◽

Qualitative Synthesis ◽

Tissue Samples

Abstract Background Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. We conducted a systematic review, including both a qualitative synthesis and a meta-analysis, to synthesize the evidence from the epidemiological literature on the association between F. nucleatum detection in the colon/rectum and CRC. Methods A systematic literature search of Ovid MEDLINE(R), Embase, Web of Science Core Collection, EBM Reviews—Cochrane Database of Systematic Reviews, and CINAHL Plus with Full Text was conducted using earliest inclusive dates up to 4 October 2020. Eligible studies were original, comparative observational studies that reported results on colorectal F. nucleatum detection and CRC. Two independent reviewers extracted the relevant information. Odds ratio (OR) estimates were pooled across studies using the random effects model. Newcastle-Ottawa scale was used to critically appraise study quality. Results Twenty-four studies were included in the systematic review, of which 12 were included in the meta-analysis. Studies investigated F. nucleatum in feces, colorectal tissue samples, or both. In most studies included in the systematic review, the load of F. nucleatum was higher, on average, in specimens from CRC patients than in those from CRC-free controls. Meta-analysis showed a positive association between F. nucleatum detection in colorectal specimens and CRC (OR = 8.3; 95% confidence interval (95% CI) 5.2 to 13.0). Conclusions The results of this systematic review suggest that F. nucleatum in the colon/rectum is associated with CRC. Systematic review registration This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018 (registration number CRD42018095866).

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INHIBITION OF COX-2 EXPRESSION BY LUNASIN-RICH SOYBEAN EXTRACT ON COLORECTAL CANCER

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019.v11s6.33572 ◽

2019 ◽

pp. 116-121

Author(s):

KUSMARDI KUSMARDI ◽

VANNESSA KARENINA ◽

ARI ESTUNINGTYAS ◽

ARYO TEDJO

Keyword(s):

Colorectal Cancer ◽

Distal Colon ◽

Negative Control Group ◽

Negative Control ◽

Colorectal Carcinogenesis ◽

Control Group ◽

Tissue Samples ◽

Cell Counts ◽

Soybean Extract ◽

Cox 2

Objective: The incidence of colorectal cancer has been growing faster than most other cancers in the past decade, especially in developing countries. One of the substances that is currently being investigated as potential chemopreventive agent is lunasin, which is contained in soybeans. This research explored the effect of lunasin on COX-2 expression in the distal colons of mice in which colorectal carcinogenesis was induced with azoxymethane (AOM) and dextran sodium sulfate (DSS). Methods: A total of 30 Swiss Webster mice were separated into six groups. In five of the groups—a negative control group, positive control group, and three intervention groups—carcinogenesis was induced with AOM and DSS; the sixth group received no interventions. Lunasin-rich soybean extracts were given in doses of 250, 300, and 350 mg/kgBW for 6 w to the intervention groups Immunohistochemical staining of COX-2 was then carried out on tissue samples from the distal colons of mice that had been sacrificed. The samples were microscopically assessed and photographed, and cell counts were performed using the Image J application. COX-2 expression is reported in the form of an optical density score (ODS). Results: Significant differences between the negative control and the intervention groups were found at the 300 mg/kgBW (p = 0.047) and 350 mg/kgBW (p = 0.016) lunasin dosage levels. Conclusions: This demonstrates that administration of lunasin-rich soy extracts can inhibit COX-2 expression in cryptic epithelial cells of the distal colon in mice with carcinogenesis induced by AOM and DSS.

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