Forkhead Box Q1 Expression Is Associated With Tumor Location of Right-Sided Colon, But Not With Acquisition of Oxaliplatin Resistance in Colorectal Cancer

2021 ◽  
Author(s):  
Tomoki Yamano ◽  
Shuji Kubo ◽  
Tomoko Kominato ◽  
Aya Yano ◽  
Yuya Takenaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Standard Treatment ◽  
Tumor Location ◽  
Resistance Mechanisms ◽  
Normal Colonic Mucosa ◽  
Recurrent Colorectal Cancer ◽  
Forkhead Box ◽  
The Right ◽  
Sirna Knockdown

Abstract Oxaliplatin (OHP) is a reagent for the standard treatment of advanced and recurrent colorectal cancer (CRC), although OHP resistance mechanisms are not fully elucidated. We found that OHP-resistant clones derived from HCT116, but not DLD1 were also resistant against the other drugs used for CRC treatment (5-fluorouracil, OHP, and trifluorothymidine) and their xenograft tumors were resistant against OHP treatment. Among the candidate genes derived from microarray analysis using the samples of OHP-resistant cells and their xenografts derived from HCT116, Forkhead box Q1 (FOXQ1) was further assessed for validation of OHP resistance and its association with clinicopathological features. Modification of FOXQ1 via siRNA knockdown and expression vector could not confirm the involvement of FOXQ1 in OHP resistance. In 173 CRC patients, FOXQ1 was upregulated in most CRC tumors compared to normal colonic mucosa. FOXQ1 expression was significantly different by tumor location of the right-sided colon cancer compared with left-sided and rectal cancer. Moreover, expression level was significantly associated with prognosis in advanced and recurrent patients. TCGA data also showed significant association of FOXQ1 expression with tumor location. Our results indicated that FOXQ1 expression is associated with tumor location of right-sided colon, but not with acquisition of OHP resistance in colorectal cancer.

Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
High Density ◽  
Prognostic Indicators ◽  
Normal Colonic Mucosa ◽  
Solid Cancer ◽  
Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin E ◽  
Vitamin C ◽  
Colonic Mucosa ◽  
Genetic Alterations ◽  
Colorectal Carcinogenesis ◽  
Normal Colonic Mucosa ◽  
Antioxidant Agents ◽  
Β Carotene

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

scholarly journals An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis

2017 ◽  
Vol 16 ◽  
pp. 117693511771640 ◽  
Author(s):  
Martha L Slattery ◽  
Jennifer S Herrick ◽  
John R Stevens ◽  
Roger K Wolff ◽  
Lila E Mullany
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Colonic Mucosa ◽  
Target Gene ◽  
Target Genes ◽  
Multiple Comparisons ◽  
Normal Colonic Mucosa ◽  
Seed Region ◽  
Discovery Phase

Background: Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes. Methods: We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miRNAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations. Results: From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37, respectively. Conclusions: Our data suggest that miRNA target gene databases are incomplete; pathways derived from these databases have similar deficiencies. Although we know a lot about several miRNAs, little is known about other miRNAs in terms of their targeted genes. We encourage others to use their data to continue to further identify and validate miRNA-targeted genes.

MGMT methylation is associated primarily with the germline C>T SNP (rs16906252) in colorectal cancer and normal colonic mucosa

2009 ◽  
Vol 22 (12) ◽  
pp. 1588-1599 ◽  
Author(s):  
Nicholas J Hawkins ◽  
James H-F Lee ◽  
Justin J-L Wong ◽  
Chau-To Kwok ◽  
Robyn L Ward ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Mgmt Methylation

scholarly journals Comparative analysis of exosome markers and extracellular vesicles between colorectal cancer and cancer-associated normal colonic mucosa

2020 ◽  
Author(s):  
Łukasz Zadka ◽  
Aleksandra Piotrowska ◽  
Agnieszka Opalińska ◽  
Katarzyna Haczkiewicz-Leśniak ◽  
Damian Grybowski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Comparative Analysis ◽  
Extracellular Vesicles ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa

Epigenetic events in normal colonic mucosa surrounding colorectal cancer lesions

2008 ◽  
Vol 44 (17) ◽  
pp. 2689-2695 ◽  
Author(s):  
N. Ramírez ◽  
E. Bandrés ◽  
A. Navarro ◽  
A. Pons ◽  
S. Jansa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Epigenetic Events

scholarly journals Complete Regression of Giant Inflammatory Polyp after Treatment with Adalimumab

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Antoine Abou Rached ◽  
Leila El Masri ◽  
Mary Nakhoul
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Rare Complication ◽  
Normal Colonic Mucosa ◽  
Complete Regression ◽  
Complete Disappearance ◽  
Biologic Treatment ◽  
Inflammatory Polyp ◽  
First Case

Giant inflammatory polyps (GIPs) are a rare complication of IBD resulting from chronic regenerative and healing processes leading to a polypoid formation on inflamed mucosa. We reported a case of GIP in a patient with long standing left-sided ulcerative colitis (UC); a well circumscribed sessile GIP was found during a colonoscopy for colorectal cancer screening on a normal colonic mucosa in the cecum. After a severe flare of the left-sided colitis and due to partial response to steroids patient was treated with adalimumab; new colonoscopy after 6 months shows complete disappearance of the GIP previously described. It is the first case report of GIP in normal macroscopic mucosa with complete disappearance after biologic treatment.

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